Follicular variant of papillary thyroid carcinoma (FVPTC), particularly the encapsulated subtype, often causes a diagnostic dilemma. We reconfirmed the molecular profiles in a large number of FVPTCs and investigated the efficacy of the preoperative mutational analysis in indeterminate thyroid nodules. BRAF V600E/K601E and RAS mutational analysis was performed on 187 FVPTCs. Of these, 132 (70.6%) had a point mutation in one of the BRAF V600E (n = 57), BRAF K601E (n = 11), or RAS (n = 64) genes. All mutations were mutually exclusive. The most common RAS mutations were at NRAS codon 61. FNA aspirates from 564 indeterminate nodules were prospectively tested for BRAF and RAS mutation and the surgical outcome was correlated with the mutational status. Fifty-seven and 47 cases were positive for BRAF and RAS mutation, respectively. Twenty-seven RAS-positive patients underwent surgery and all except one patient had FVPTC. The PPV and accuracy of RAS mutational analysis for predicting FVPTC were 96% and 84%, respectively. BRAF or RAS mutations were present in more than two-thirds of FVPTCs and these were mutually exclusive. BRAF mutational analysis followed by N, H, and KRAS codon 61 mutational analysis in indeterminate thyroid nodules would streamline the management of patients with malignancies, mostly FVPTC.
Background. DNA methyltransferase 3A (DNMT3A) mutation was recently introduced as a prognostic indicator in normal karyotype (NK) AML and we evaluated the incidence and prognostic impact of DNMT3A mutations in Korean NK AML patients. Methods. Total 67 NK AML patients diagnosed during the recent 10 years were enrolled. DNMT3A mutations were analyzed by direct sequencing and categorized into nonsynonymous variations (NSV), deleterious mutations (DM), and R882 mutation based on in silico analysis results. Clinical features and prognosis were compared with respect to DNMT3A mutation status. Results. Three novel (I158M, K219V, and E177V) and two known (R736H and R882H) NSVs were identified and the latter three were predicted as DMs. DNMT3A NSVs, DMs, and R882 mutation were identified in 14.9%–17.9%, 10.3%–10.4%, and 7.5% of patients, respectively. DNMT3A mutations were frequently detected in FLT3 ITD mutated patients (P = 0.054, 0.071, and 0.071 in NSV, DMs, and R882 mutation, resp.) but did not affect clinical features and prognosis significantly. Conclusions. Incidences of DNMT3A NSVs, DMs, and R882 mutation are 14.9%–17.9%, 10.3%–10.4%, and 7.5%, respectively, in Korean NK AML patients. DNMT3A mutations are associated with FLT3 ITD mutations but do not affect clinical outcome significantly in Korean NK AML patients.
We report three patients with normal karyotype (NK) ALL, who showed genetic aberrations as determined by high-resolution single nucleotide polymorphism array (SNP-A) analysis at both diagnosis and relapse. We evaluated the clinical relevance of the SNP-A assay for the detection of subtle changes in the size of affected genetic lesions at relapse as well as the prognostic value of the assay. In our patients, application of the SNP-A assay enabled sensitive detection of cryptic changes affecting clinically important genes in NK ALL. Therefore, this assay seems to be more advantageous compared to other conventional methods such as FISH assay, HemaVision (DNA Technology, Denmark), and conventional karyotyping for the detection of an "unstable genotype" at relapse, which may be associated with microscopic clonal evolution and poor prognosis. Further comprehensive studies are required to confirm the issues presented by our case patients in this report.
Acute lymphoblastic leukemia; Array; Clonal evolution; Normal karyotype; Prognosis; Single nucleotide polymorphism
Peroxisome proliferator-activated receptor gamma (PPARγ) was identified as a cell-intrinsic regulator of Th17 cell differentiation. Th17 cells have been associated with several autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), inflammatory bowel disease (IBD), and collagen-induced arthritis. In this study, we confirmed PPARγ-mediated inhibition of Th17 cell differentiation and cytokine production at an early stage. Treatment with ciglitazone, a PPARγ ligand, reduced both IL-1β-mediated enhancement of Th17 differentiation and activation of Th17 cells after polarization. For Th17 cell differentiation, we found that ciglitazone-treated cells had a relatively low proliferative activity and produced a lower amount of cytokines, regardless of the presence of IL-1β. The inhibitory activity of ciglitazone might be due to decrease of CCNB1 expression, which regulates the cell cycle in T cells. Hence, we postulate that a pharmaceutical PPARγ activator might be a potent candidate for treatment of Th17-mediated autoimmune disease patients.
Th17 cell; IL-17; PPARγ; CCNB1; Cell proliferation
Wound healing is an interaction of a complex signaling cascade of cellular events, including inflammation, proliferation, and maturation. K+ channels modulate the mitogen-activated protein kinase (MAPK) signaling pathway. Here, we investigated whether K+ channel-activated MAPK signaling directs collagen synthesis and angiogenesis in wound healing.
The human skin fibroblast HS27 cell line was used to examine cell viability and collagen synthesis after potassium chloride (KCl) treatment by Cell Counting Kit-8 (CCK-8) and western blotting. To investigate whether K+ ion channels function upstream of MAPK signaling, thus affecting collagen synthesis and angiogenesis, we examined alteration of MAPK expression after treatment with KCl (channel inhibitor), NS1619 (channel activator), or kinase inhibitors. To research the effect of KCl on angiogenesis, angiogenesis-related proteins such as thrombospondin 1 (TSP1), anti-angiogenic factor, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), pro-angiogenic factor were assayed by western blot.
The viability of HS27 cells was not affected by 25 mM KCl. Collagen synthesis increased dependent on time and concentration of KCl exposure. The phosphorylations of MAPK proteins such as extracellular-signal-regulated kinase (ERK) and p38 increased about 2.5-3 fold in the KCl treatment cells and were inhibited by treatment of NS1619. TSP1 expression increased by 100%, bFGF expression decreased by 40%, and there is no significant differences in the VEGF level by KCl treatment, TSP1 was inhibited by NS1619 or kinase inhibitors.
Our results suggest that KCl may function as a therapeutic agent for wound healing in the skin through MAPK signaling mediated by the K+ ion channel.
Potassium channels; Mitogen activated protein kinases; Wound healing; Angiogenesis
The eyelid and canthal areas are common locations for cutaneous tumors. The medial canthus includes, among many other apparatuses, the canthal tendon and lacrimal canaliculi, and its characteristic thin and supple skin is hard to mimic and restore using tissue from other regions. Accordingly, reconstruction of the canthal area can prove challenging for surgeons. Although various methods, such as skin grafts and local flaps from adjacent regions, have been utilized for reconstructive purposes, they present known disadvantages. However, we were able to successfully reconstruct both lateral and medial canthal area defects by using orbicularis oculi myocutaneous island flaps.
Our study included seven patients who underwent medial or lateral canthal region reconstruction, using orbicularis oculi myocutaneous island flaps, between 2011 and 2014, following either cutaneous tumor excision or traumatic avulsion injury.
Five patients had basal cell carcinoma, one had squamous cell carcinoma of the eyelid, and one had sustained a traumatic avulsion injury of the eyelid and canthal area. Entire flap loss was not observed in any patient, but one-a heavy smoker-showed partial flap loss, which healed with secondary intention and yielded acceptable results. Donor site morbidity was not observed, and all patients were satisfied with their surgical outcomes.
The canthal regions can be successfully reconstructed with orbicularis oculi myocutaneous island flaps. These flaps offer several key advantages, including similarity in texture, color, and thickness to the recipient site and a negligible incidence of donor site morbidity.
Eyelids; Carcinoma; Myocutaneous flaps
The purpose of this study was to investigate the aortic isthmus (AoI) flow difference between larger fetus and smaller fetus of twin; and to evaluate the predictive value of early diagnosis of hemodynamic change in twin growth.
This prospective study on 49 pairs of twin fetuses was performed to obtain AoI blood flow data. Cases with structural or chromosomal abnormalities and co-twin death were excluded. The interval from examination to delivery was within 4 weeks and 3 cases over 4 weeks interval were re-examined. Assessment of fetal AoI Doppler parameters were peak systolic velocity (PSV), end-diastolic velocity, times-averaged maximum velocities, pulsatility index (PI), and resistance index (RI). According to the direction of the diastolic flow in the AoI, antegrade and retrograde flow were made and was used to analyze the perinatal outcomes of each fetus. The predictive value of AoI Doppler parameters in predicting fetal growth was obtained by using ANOVA and logistic regression analysis of quantitative variables in each fetus of twins.
There were significant differences in the gestational weeks at delivery, birth weight and the incidence of growth discordance over 20% or more between monochorionic twin and dichorionic twin. The AoI PI and RI were significantly higher in smaller fetus than in larger regardless of chorionicity. Retrograde flow was noted in 8 of 98 cases (8.2%) and the only one case was of the larger fetus and the others were smaller fetuses of twin. Significant correlations were found between the AoI PI and birthweight (P=0.018) and between the PSV and growth discordance (P=0.032). In monochorionic twin, linear correlation was shown between the AoI PI and birthweight (P=0.004) and between AoI PI and growth discordance (P=0.031). Also, the meaningful correlation between the PSV and birthweight (P=0.036) was found by using logistic regression analyses.
On the basis of our observation, AoI PI has revealed their hemodynamic status and this result may improve the understanding of growth patterns in twins.
Aortic isthmus; Chorionicity; Doppler; Growth discordance; Twins
To investigate clinical factors affecting the timing of delivery in twin pregnancies in order to minimize perinatal complications.
A retrospective study involved 163 twin pregnancies delivered from January 2006 to September 2011 at Gachon University Gil Medical Center. These cases were divided into three groups based on the delivery timing: less than 32 weeks' gestation (group A), between 32 and 35+6 weeks' gestation (group B), and over 36 weeks' gestation (group C). Clinical factors including maternal age, parity, presence of premature uterine contraction, presence of premature rupture of membrane, white blood cell, high sensitive C-reactive protein level, cervical dilatation, maternal complication, chorionicity, twin specific complication, and perinatal complication were analyzed for each group.
In group B, the timing of delivery was postponed for 14 days or more from the time of admission, and there were fewer numbers of babies with low Apgar score at birth compared with other groups. The frequency of uterine contraction (P<0.001), presence of premature rupture of membranes (P=0.017), dilatation of cervix (P<0.001), increased white blood cell and high sensitive C-reactive protein levels (P=0.002, P<0.001) were important clinical factors during decision making process of delivery timing in twin pregnancies. Twin specific fetal conditions, such as twin-twin transfusion syndrome and discordant growth (over 25% or more) were shown more frequently in group A. However, there were no significant statistical differences among three groups (P=0.06, P=0.14).
Proper management for preventing premature contraction and inflammation can be essential in twin pregnancies until 32 weeks' gestation, and may decrease maternal and perinatal complications.
Maternal complications; Perinatal complications; Timing of delivery; Twins
Currently, intensive lipid lowering is recommended in patients with atherosclerotic ischemic stroke or transient ischemic attack. However, the role of statin in cardioembolic stroke is unclear. We investigated the association of statin with pretreatment collateral status in cardioembolic stroke.
A collaborative study from two stroke centers in distinct geographic regions included consecutive patients with acute middle cerebral artery (MCA) infarction due to atrial fibrillation (AF) who underwent cerebral angiography. The relationship between pretreatment collateral grade and the use/dose of statin at stroke onset was assessed. The angiographic collateral grade was evaluated according to the ASITN/SIR Collateral Flow Grading System.
Ninety-eight patients (76 statin-naïve, 22 statin users) were included. Compared with statin-naïve patients, statin users were older and more frequently had hypertension, hyperlipidemia and coronary heart disease. Excellent collaterals (grade 3–4) were more frequently observed in statin users (11 patients, 50%) than in statin-naïve patients (21 patients, 27.6%; p = 0.049). The use of atorvastatin 10 mg equivalent or higher doses of statin was associated with excellent collaterals (p for trend = 0.025). In multiple regression analysis, prestroke statin use was independently associated with excellent collaterals (odds ratio, 7.841; 95% confidence interval, CI, 1.96–31.363; p = 0.004).
Premorbid use of statin in AF patients is associated with excellent collateral flow. Although most statin trials excluded patients with cardioembolic stroke, our data suggests the possibility that statin may be beneficial in AF-related stroke.
Atrial fibrillation; Collateral flow; Stroke; Statin; Arteriogenesis
We performed customer satisfaction surveys for physicians and nurses regarding clinical laboratory services, and for outpatients who used phlebotomy services at a tertiary care unit level to evaluate our clinical laboratory and phlebotomy services. Thus, we wish to share our experiences with the customer satisfaction survey for clinical laboratory and phlebotomy services. Board members of our laboratory designed a study procedure and study population, and developed two types of questionnaire. A satisfaction survey for clinical laboratory services was conducted with 370 physicians and 125 nurses by using an online or paper questionnaire. The satisfaction survey for phlebotomy services was performed with 347 outpatients who received phlebotomy services by using computer-aided interviews. Mean satisfaction scores of physicians and nurses was 58.1, while outpatients' satisfaction score was 70.5. We identified several dissatisfactions with our clinical laboratory and phlebotomy services. First, physicians and nurses were most dissatisfied with the specimen collection and delivery process. Second, physicians and nurses were dissatisfied with phlebotomy services. Third, molecular genetic and cytogenetic tests were found more expensive than other tests. This study is significant in that it describes the first reference survey that offers a survey procedure and questionnaire to assess customer satisfaction with clinical laboratory and phlebotomy services at a tertiary care unit level.
Customer satisfaction survey; Clinical laboratory; Phlebotomy; Service
The objective of this article is to evaluate clinical outcomes of combined orbital floor and medial wall fracture repair using a three-dimensional pre-bent titanium implant in an East Asian population.
Clinical and radiologic data were analyzed for 11 patients with concomitant orbital floor and medial wall fractures. A combined transcaruncular and inferior fornix approach with lateral canthotomy was used for the exposure of fractures. An appropriate three-dimensional preformed titanium implant was selected and inserted according to the characteristics of a given defect.
Follow-up time ranged from 2 to 6 months (median, 4.07 months). All patients had a successful treatment outcome without any complications. Clinically significant enophthalmos was not observed after treatment.
Three-dimensional pre-bent titanium implants are appropriate for use in the East Asian population, with a high success rate of anatomic restoration of the orbital volume and prevention of enophthalmos in combined orbital floor and medial wall fracture cases.
Orbital fractures; Enophthalmos; Orbital implant
The differential diagnosis of cardiac mass is important in determining the therapeutic plan and avoiding unnecessary surgical intervention. Non-invasive imaging methods would be useful in the diagnosis of suspected cardiac mass, because they may provide earlier diagnosis and more accurate assessment of cardiac mass. Native aortic valve thrombosis is a rare disorder and difficult to differentiate from a tumor, and in particular, a papillary fibroelastoma. Thus, the clinical decision making with imaging modalities should be performed cautiously. We recently met a female patient who had a aortic valve mass resembling papillary fibroelastoma in normal native valve. The patient underwent a surgical resection and the pathologic finding showed an organized thrombus with no evidence of papillary fibroelastoma.
Thrombosis; Aortic valve; Pulmonary embolism
It is well known that lead exposure induces neurotoxic effects, which can result in a variety of neurocognitive dysfunction. Especially, occupational lead exposures in adults are associated with decreases in cognitive performance including working memory. Despite recent advances in human neuroimaging techniques, the neural correlates of lead-exposed cognitive impairment remain unclear. Therefore, this study was aimed to compare the neural activations in relation to working memory function between the lead-exposed subjects and healthy controls.
Thirty-one lead-exposed subjects and 34 healthy subjects performed an n-back memory task during MRI scan. We performed fMRI using the 1-back and 2-back memory tasks differing in cognitive demand. Functional MRI data were analyzed using within- and between-group analysis. We found that the lead-exposed subjects showed poorer working memory performance during high memory loading task than the healthy subjects. In addition, between-group analyses revealed that the lead-exposed subjects showed reduced activation in the dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, pre supplementary motor areas, and inferior parietal cortex.
Our findings suggest that functional abnormalities in the frontoparietal working memory network might contribute to impairments in maintenance and manipulation of working memory in the lead-exposed subjects.
Oncogenic mutational analysis provides predictive guidance for therapeutics such as anti-EGFR antibodies, but it is successful only for a subset of colorectal cancer (CRC) patients.
A comprehensive molecular profiling of 120 CRC patients, including 116 primary, 15 liver metastasis, and 1 peritoneal seeding tissue samples was performed to identify the relationship between v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) WT and mutant CRC tumors and clinical outcomes. This included determination of the protein activation patterns of human epidermal receptor 1 (HER1), HER2, HER3, c-MET, insulin-like growth factor 1 receptor (IGF1R), phosphatidylinositide 3-kinase (PI3K), Src homology 2 domain containing (Shc), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK) kinases using multiplexed collaborative enzyme enhanced reactive (CEER) immunoassay.
KRAS WT and mutated CRCs were not different with respect to the expression of the various signaling molecules. Poor prognosis in terms of early relapse (<2 years) and shorter disease-free survival (DFS) correlated with enhanced activation of PI3K signaling relative to the HER kinase pathway signaling, but not with the KRAS mutational status. KRAS WT CRCs were identified as a mixed prognosis population depending on their level of PI3K signaling. KRAS WT CRCs with high HER1/c-MET index ratio demonstrated a better DFS post-surgery. c-MET and IGF1R activities relative to HER axis activity were considerably higher in early relapse CRCs, suggesting a role for these alternative receptor tyrosine kinases (RTKs) in driving high PI3K signaling.
The presented data subclassified CRCs based on their activated signaling pathways and identify a role for c-MET and IGF1R-driven PI3K signaling in CRCs, which is superior to KRAS mutational tests alone. The results from this study can be utilized to identify aggressive CRCs, explain failure of currently approved therapeutics in specific CRC subsets, and, most importantly, generate hypotheses for pathway-guided therapeutic strategies that can be tested clinically.
Lymphangioma is a rare, benign mesenchymal neoplasm, which is characterized by numerous intercommunicating cystic spaces containing lymphatic fluid. It is considered a congenital disease resulting from the obstruction of regional lymph drainage during the developmental period. Lymphangioma may be focal/unilateral or diffuse/bilateral, and in the latter case, it is referred to as lymphangiomatosis. Here, we report a case of a 38-year-old man with perirenal lymphangiomatosis. The patient's chief complaint was left flank pain, and left pleural effusion was found on radiological examination. After radical nephrectomy, the pathological examinations revealed that the kidney was enclosed by a multicystic mass with intrarenal cystic dilatations. We report the case and discuss the management of perirenal lymphangiomatosis with a literature review.
Kidney; Lymphangioma; Lymphatic diseases; Neoplasms
Neurogenic pulmonary edema (NPE) in brain dead organ donors occurring after an acute central nervous system insult threatens organ preservation of potential organ donors and the outcome of organ donation. Hence the active and immediate management of NPE is critical. In this case, a 50-year-old male was admitted to the intensive care unit (ICU) for organ donation. He was hypoxic due to NPE induced by spontaneous intracerebral hemorrhage and intraventricular hemorrhage. Protective ventilatory management, intermittent recruitment maneuvers, and supportive treatment were maintained in the ICU and the operating room (OR). Despite this management, the hypoxemia worsened after the OR admission. So inhaled nitric oxide (NO) therapy was performed during the operation, and the hypoxic phenomena showed remarkable improvement. The organ retrieval was successfully completed. Therefore, NO inhalation can be helpful in the improvement of hypoxemia caused by NPE in brain dead organ donors during anesthesia for the organ donation.
Brain death; Nitric oxide; Organ donors; Organ retrieval; Pulmonary edema
To access the effectiveness of radiofrequency myolysis (RFM) in women with midline dysmenorrhea.
We designed RFM in two ways laparoscopic RFM (LRFM), vaginal ultrasound-guided RFM (URFM). One hundred and thirty-two patients were in the LRFM group and, 140 patients were in the URFM group.
Upon receipt of surgery, both the LRFM and the URFM groups demonstrated a significant decrease (P < 0.001) in the mean pain score when compared to those before and after surgery.
The RF uterine myolysis procedure provides an alternative for those patients who suffer from intractable midline dysmenorrhea. LRFM is an alternative choice because it is relatively safe and, simple to perform and moreover, it is satisfactory. LRFM appears to increasingly succeed in the treatment of midline dysmenorrhea.
Dysmenorrhea; Laparoscopy; Leiomyoma; Radiofrequency myolysis; Ultrasonography
Congenital leukemia is very rare, and its prevalence according to recently published papers is from 1 to 5 per million live births. This can be often diagnosed in postpartum throughout bone marrow biopsy, showing abnormal proliferation of immature blasts and granulocytic precursors. Hepatosplenomegaly is the most common feature which is found during perinatal examinations, that diagnosing is difficult during perinatal period. Hepatosplenomegaly can occur not only in congenital leukemia but in many other cases such as infection which is the most common cause. In other words, congenital leukemia is the one of the rare causes of hepatosplenomegaly. However, this case shows the fetus with the features of hepatosplenomegaly during perinatal period and being diagnosed as congenital leukemia associated with acquired AML1 gene duplication in postpartum through bone marrow biopsy. Due to its rare instance, we are to describe the case with a review of literatures.
AML1 gene; Duplication; Congenital leukemia; Fetal; Hepatosplenomegaly
Encephalitozoon cuniculi is a microsporidian parasite commonly found in rabbits that can infect humans, causing encephalitozoonosis. The prevalence of encephalitozoonosis is not well documented, even when many clinics suspect pet rabbits as being highly infected. This study investigated the seropositivity of E. cuniculi using ELISA. The examination of 186 rabbits using ELISA showed that 22.6% (42/186) were seropositive against E. cuniculi. In analysis with healthy status, all 42 seropositive sera were collected from clinically normal rabbits. Moreover, the gender and age of pet rabbits did not have anysignificant effect on E. cuniculi infection. To the best of our knowledge, this is the first report to describe the seroprevalence of E. cuniculi in pet rabbits and suggests that pet rabbits could act as an important reservoir of encephalitozoonosis for both pet animals and humans in Korea.
Encephalitozoon cuniculi; pet rabbit; seroprevalence
Mexican American (MA) elders are more functionally impaired at younger ages than other elders yet use home care services (HCS) less. To determine possible reasons, nine questionnaires were completed in Spanish or English by MA elders and caregivers living in southern Arizona (n=280). Contextual, personal, and attitudinal factors were significantly associated with use of HCS; and cultural/ethnic factors were significantly associated with confidence in HCS. Interventions should be designed and tested to increase use of HCS by Mexican American elders, by increasing service awareness and confidence in HCS, while preserving expectations of familism and reducing caregiving burden.
utilization; home care services; Mexican American elders; family caregiving
The Ministry of Health and Welfare and the Korea Centers for Disease Control and Prevention in South Korea have been organizing hepatitis B virus (HBV) vertical infection prevention projects since July 2002. In this single-institute study, the results of surveys conducted in target mothers who delivered babies in a tertiary hospital were investigated and analyzed.
Of the 9,281 mothers and their 9,824 neonates born between July 2002 and December 2012, 308 hepatitis B surface antigen (HBsAg)-positive mothers and their 319 neonates were selected for this study, and their records were analyzed retrospectively.
A total of 308 mothers were HBsAg-positive, with an HBV prevalence of 3.32% (308/9,281). There were 319 neonates born to these HBsAg-positive mothers, and 252 were confirmed to as either HBsAg-positive or -negative. Four were confirmed as HBsAg-positive, with a 1.59% (4/252) HBV vertical infection rate. All the mothers of neonates who had an HBV vertical infection were hepatitis B e antigen (HBeAg)-positive. Among the HBsAg-positive neonates, three were HBeAg-positive and had an HBV DNA titer of 1.0 × 108 copies/mL.
The HBV prevalence of mothers was 3.32% (308/9,281), and their vertical infection rate was 1.59% (4/252). Thus, the South Korean HBV vertical infection prevention projects are effective, and, accordingly, HBV prevalence in South Korea is expected to decrease continuously.
Hepatitis B; Vaccination; Vertical infection transmission; Korea
Multiplex genome engineering is a standalone recombineering tool for large-scale programming and accelerated evolution of cells. However, this advanced genome engineering technique has been limited to use in selected bacterial strains. We developed a simple and effective strain-independent method for effective genome engineering in Escherichia coli. The method involves introducing a suicide plasmid carrying the λ Red recombination system into the mutS gene. The suicide plasmid can be excised from the chromosome via selection in the absence of antibiotics, thus allowing transient inactivation of the mismatch repair system during genome engineering. In addition, we developed another suicide plasmid that enables integration of large DNA fragments into the lacZ genomic locus. These features enable this system to be applied in the exploitation of the benefits of genome engineering in synthetic biology, as well as the metabolic engineering of different strains of E. coli.
Background and Purpose
Oxidative stress is involved in the pathophysiological mechanisms of stroke (e.g., atherosclerosis) and brain injury after ischemic stroke. Statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, have both pleiotropic and low-density lipoprotein (LDL)-lowering properties. Recent trials have shown that high-dose statins reduce the risk of cerebrovascular events. However, there is a paucity of data regarding the changes in the oxidative stress markers in patients with atherosclerotic stroke after statin use. This study evaluated changes in oxidative stress markers after short-term use of a high-dose statin in patients with atherosclerotic stroke.
Rosuvastatin was administered at a dose of 20 mg/day to 99 patients who had suffered an atherosclerotic stroke and no prior statin use. Blood samples were collected before and 1 month after dosing, and the serum levels of four oxidative stress markers-malondialdehyde (MDA), oxidized LDL (oxLDL), protein carbonyl content (PCO), and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-were evaluated to determine the oxidation of MDA and lipids, proteins, and DNA, respectively, at both of those time points.
The baseline levels and the degrees of reduction after statin use differed among the oxidative stress markers measured. MDA and PCO levels were associated with infarct volumes on diffusion-weighted imaging (r=0.551, p<0.05, and r=0.444, p=0.05, respectively). Statin use decreased MDA and oxLDL levels (both p<0.05) but not the PCO or 8-OHdG level. While the reduction in MDA levels after statin use was not associated with changes in cholesterol, that in oxLDL levels was proportional to the reductions in cholesterol (r=0.479, p<0.01), LDL (r=0.459, p<0.01), and apolipoprotein B (r=0.444, p<0.05).
The impact of individual oxidative stress markers differs with time after ischemic stroke, suggesting that different oxidative markers reflect different aspects of oxidative stress. In addition, short-term use of a statin exerts antioxidant effects against lipid peroxidation via lipid-lowering-dependent and -independent mechanisms, but not against protein or DNA oxidation in atherosclerotic stroke patients.
atherosclerosis; ischemic stroke; statin; oxidative stress; cholesterol
We report a case of a 74-year-old female with myxoid adrenocortical adenoma which showed different magnetic resonance imaging findings compared to those of a typical adrenocortical adenoma. The myxoid change in the adrenocortical adenoma is a rare form of degeneration. It presents a considerable diagnostic challenge to both radiologists and clinicians because it can mimic other adrenal tumor types on imaging. The MRI findings of the presented case included a high signal intensity on T2-weighted images similar to that of fluid and delayed progressive enhancement.
Adrenocortical adenoma; Myxoid; MRI