Synthesis of 3'-O-fluorescently mono-modified reversible terminators and their uses in sequencing-by-synthesis.

Next-generation sequencing (NGS) technologies recently developed are now used for study of genomes from various organisms. Sequencing-by-synthesis (SBS) is a key strategy in the NGS. The SBS uses nucleotides so-called dual-modified reversible terminators (DRTs) in which bases are labeled with fluorophores and 3'-OH is protected with a reversibly cleavable chemical group, respectively. In this study, we examined the possibility of performing SBS with mono-modified reversible terminators (MRTs), in which the reversible blocking group on the 3'-OH plays a dual role as a fluorescent signal report as well as a chemical protection. We studied cyclic reversible termination by using two MRTs (dA and dT), wherein the modifications were two different fluorophores and cleavable to regenerate a free 3'-OH. We here demonstrated that SBS could be achieved with incorporation of MRTs by a DNA polymerase and correct base-calls based on the two different colors from the fluorophores.

Inhibition of VEGF transcription through blockade of the hypoxia inducible factor-1α-p300 interaction by a small molecule.

Vascular endothelial growth factor (VEGF) plays a pro-angiogenic role in tumor progression. Stabilization of a key regulator termed the hypoxia inducible factor (HIF)-1α under oxygen deficient environment around tumor is known to elicit expression of VEGF through binding to p300. Thus, inhibition of the HIF-1α-p300 interaction would lead to down-regulation of VEGF expression, thereby providing potential cancer therapeutics. Here, we have screened a chemical library against the interaction of the HIF-1α-derived peptide with p300 employing a fluorescence polarization-based assay. We have identified a compound as the most prominent inhibitor against the protein-protein interaction. Further, we have observed suppression of the mRNA level of VEGF upon treatment of HeLa cells with the compound, demonstrating its inhibitory effect at the cellular level.

Conversion from acetate dialysate to citrate dialysate in a central delivery system for maintenance hemodialysis patients.

BACKGROUND: The objective of this study was to compare the impact of citrate dialysate (CD) and standard acetate dialysate (AD) in hemodialysis by central delivery system (CDS) on heparin demand, and clinical parameters. METHODS: We retrospectively evaluated 75 patients on maintenance hemodialysis with CDS. Patients underwent hemodialysis with AD over a six-month period (AD period), followed by another six-month period using CD (CD period). Various parameters including mean heparin dosage, high sensitivity C-reactive protein (hsCRP), calcium-phosphate product (CaxP), intact parathyroid hormone (iPTH), and urea reduction ratio (URR) were collated at the end of each period. RESULTS: Patients were 60.5 ± 14.7 years old, of whom 62.7% were male. Patients required less heparin when receiving CD (AD period: 1,129 ± 1,033 IU/session vs. CD period: 787 ± 755 IU/session, P < 0.001). After the CD period (ΔCD), pre-dialysis total CO2 increased to 1.21 ± 2.80 mmol/L, compared to -2.44 ± 2.96 mmol/L (P < 0.001) after the AD period (ΔAD). After the CD period, concentrations of iPTH (ΔAD: 73.04 ± 216.34 pg/mL vs. ΔCD: -106.66 ± 251.79 pg/mL, P < 0.001) and CaxP (ΔAD: 4.32 ± 16.63 mg2/dL2 vs. ΔCD: -4.67 ± 15.27 mg2/dL2, P = 0.015) decreased. While hsCRP levels decreased after the CD period (ΔAD: 0.07 ± 4.09 mg/L vs. ΔCD: -0.75 ± 4.56 mg/L, P = 0.705), the change was statistically insignificant. URR remained above clinical guideline of 65% after both periods (ΔAD: 72.33 ± 6.92% vs. ΔCD period: 69.20 ± 4.49%, P = 0.046). CONCLUSION: Our study confirmed that the use of CD in CDS required lower heparin doses compared to the use of AD. The use of CD also provided a more stable acid-base status.

Update of aristolochic acid nephropathy in Korea.

BACKGROUND/AIMS: The true incidence of aristolochic acid nephropathy (AAN) is thought to be underestimated because numerous ingredients known or suspected to contain aristolochic acid (AA) are used in traditional medicine in Korea. METHODS: We collected data on cases of AAN since 1996 via a database in Korea. We evaluated the year of AAN development, route to obtaining AA-containing herbal medicine, gender, reason for taking AA-containing herbal medicine, clinical manifestations, histological findings, phytochemical analysis, and prognosis of patients with AAN. RESULTS: Data on 16 cases of AAN were collected. Thirteen cases developed AAN before and three cases after the prohibition of AA-containing herbal medicine by the Korea Food and Drug Administration. Patients were prescribed AA-containing herbal medicine from oriental clinics or had purchased it from traditional markets. AAN was distributed in all age groups. Young females were most commonly exposed to AA-containing herbal medicine for slimming purposes and postpartum health promotion, while older adults took AA-containing compounds for the treatment of chronic diseases. The most common symptoms presented at hospitalization were nausea and vomiting, and acute kidney injury was accompanied by Fanconi syndrome in almost half of the patients. Phytochemical analysis of AA in herbal medicine was available in six cases. Progression to end stage renal disease (ESRD) was observed in seven patients (43.8%), and five patients (31.3%) had progressed to ESRD within 6 months of diagnosis. CONCLUSION: Our report shows that patients were still exposed to AA-containing herbal medicine and that there is a possibility of underdiagnosis of AAN in Korea. A stronger national supervision system of herbal ingredients and remedies in oriental medicine is needed to prevent AAN.

Ameliorating Effect of Gemigliptin on Renal Injury in Murine Adriamycin-Induced Nephropathy.

Background. Previous studies have shown the antiapoptotic and anti-inflammatory potential of DPP-IV inhibitor in experimental models of renal injury. We tested whether DPP-IV inhibitor (gemigliptin) ameliorates renal injury by suppressing apoptosis, inflammation, and oxidative stress in mice with adriamycin nephropathy. Methods. Mice were treated with normal saline (control), gemigliptin (GM), adriamycin (ADR), or adriamycin combined with gemigliptin (ADR+GM). Apoptosis, inflammation, and oxidative stress were analyzed via western blotting, real-time PCR, light microscopy, and immunofluorescence. Results. In the ADR+GM group, urine albumin creatinine ratio decreased significantly compared with that in the ADR group on day 15. Glomerulosclerosis index and tubulointerstitial injury index in mice with adriamycin-induced nephropathy decreased after gemigliptin treatment. ADR group showed higher levels of apoptosis, inflammation, and oxidative stress-related molecules compared with the control group. The upregulation of these molecules was significantly reduced by gemigliptin. In the ADR group, the staining intensities of WT-1 and nephrin reduced, but these changes were ameliorated in the ADR+GM group. Conclusion. We demonstrated that gemigliptin ameliorates nephropathy by suppressing apoptosis, inflammation, and oxidative stress in mice administered adriamycin. Our data demonstrate that gemigliptin has renoprotective effects on adriamycin-induced nephropathy.

Syndrome of inappropriate antidiuretic hormone secretion associated with seronegative neuromyelitis optica spectrum disorder.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a potential cause of hyponatremia of the central nervous system (CNS). Although SIADH has been reported to be associated with many other central nervous disorders, its association with neuromyelitis optica (NMO) or NMO spectrum disorders are rare. NMO is a demyelinating disorder characterized by optic neuritis and transverse myelitis. Aquaporin-4 (AQP4), which is the target antigen for a NMO autoantibody, is the predominant CNS water channel. However, some NMO patients show seronegative AQP4 antibody results. The spectrum of NMO has been changed, and new findings about the disease have been reported. Here, we report a case of seronegative NMO spectrum disorder associated with SIADH.

Total Ankle Arthroplasty: An Imaging Overview.

With advances in implant technology, total ankle arthroplasty (TAA) has become an increasingly popular alternative to arthrodesis for the management of end-stage ankle arthritis. However, reports in the literature do not focus on the imaging features of TAA. Through a literature review, we demonstrate basic design features of the current ankle arthroplasty system, and the normal and abnormal postoperative imaging features associated with such devices. Pre- and postoperative evaluations of ankle arthroplasty mainly include radiography; in addition, computed tomography and magnetic resonance imaging provide further characterization of imaging abnormalities. Familiarization with multimodal imaging features of frequent procedural complications at various postoperative intervals is important in radiological practice.

Elevated serum immunoglobulin E level as a marker for progression of immunoglobulin A nephropathy.

BACKGROUND: Immunoglobulin E (IgE) has traditionally been associated with anaphylaxis and atopic disease. Previous studies reported that serum IgE levels are elevated in nephrotic syndrome and suggested IgE levels as a prognostic indicator in glomerular diseases. The aim of this study was to explore the association between serum IgE levels and renal outcome in patients with immunoglobulin A nephropathy (IgAN). METHODS: We included 117 patients with biopsy-proven IgAN. Renal progression was defined if a patient meets one of these criteria: (1) a negative value of delta estimated glomerular filtration rate (mL/min/1.73 m(2)/mo) or (2) a rise in serum creatinine to an absolute level of ≥ 1.3 mg/dL (male) or 1.2 mg/dL (female). We defined delta changes in serum creatinine, estimated glomerular filtration rate, and proteinuria as a difference of values during the follow-up period. RESULTS: A total of 117 patients with IgAN were included. The serum IgE level was significantly high in the renal progressive group compared with the nonprogressive group. Sex and history of gross hematuria were significantly different between the high-IgE group and the low-IgE group. Regression analysis showed that a male sex, initial proteinuria, and change of proteinuria were significantly associated with serum IgE levels. CONCLUSION: The serum IgE level is potentially associated with disease progression and pathogenesis of IgAN.

Comparison of two different doses of single bolus steroid injection to prevent atrial fibrillation recurrence after radiofrequency catheter ablation.

PURPOSE: Steroids may play a role in preventing the early recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA). However, optimal doses and route of steroid delivery have not yet been determined. This study evaluated the effect of two different doses of a single bolus injection of steroids on AF recurrence after RFCA. MATERIALS AND METHODS: Of 448 consecutive AF patients who underwent RFCA, a single steroid bolus was injected into 291 patients. A low-dose steroid group (n=113) received 100 mg of hydrocortisone and a moderate-dose steroid group (n=174) received 125 mg of methylprednisolone. We used propensity-score matching to select patients as follows: control (n=95), low-dose (n=95), and moderate-dose steroid groups (n=97). RESULTS: Pericarditis developed in 1 (1.1%) control patient, 2 (2.1%) low-dose patients and 0 moderate-dose patients. Maximum body temperature and C-reactive protein were significantly decreased in the moderate-dose steroid group compared to the other groups (p<0.01). The number of patients of early AF recurrence (≤3 months) did not differ among three groups. Early recurrence was 24 (25%) in the control, 24 (25%) in the low-dose and 25 (26%) in the medium-dose groups (p=0.99). Compared with control group, low-dose or moderate-dose steroid treatment did not effectively decrease mid-term (3-12 months) AF recurrence [22 (23%) vs. 23 (24%) vs. 18 (19%); p=0.12]. CONCLUSION: A single injection of moderate-dose steroid decreased inflammation. However, single bolus injections of low-dose or moderate-dose steroids were not effective in preventing immediate, early or midterm AF recurrence after RFCA.

A case of Ramsay Hunt syndrome diagnosed after kidney transplantation.

We report the first case of Ramsay Hunt syndrome (RHS) diagnosed after kidney transplantation in Korea. RHS is a disease caused by latent varicella-zoster characterized to involve geniculate ganglion of the seventh cranial nerve. Patients who have undergone kidney transplantation can be easily affected by viral infections because of their immune-compromised status. A 35-year-old man with hypertensive end-stage renal disease underwent kidney transplantation. Two months after surgery, the recipient was diagnosed with RHS and treated with antivirals and steroids. However, after using the antiviral agents for the recommended duration, facial paralysis occurred as a new presentation and he required further treatment. Otalgia and periauricular vesicles improved, but the facial palsy remained.

Drug delivery by a self-assembled DNA tetrahedron for overcoming drug resistance in breast cancer cells.

A DNA tetrahedron is employed for efficient delivery of doxorubicin into drug-resistant breast cancer cells. The drug delivered with the DNA nanoconstruct is considerably cytotoxic, whereas free doxorubicin is virtually non-cytotoxic for the drug-resistant cells. Thus, the DNA tetrahedron, made of the inherently natural and biocompatible material, can be a good candidate for the drug carrier to overcome MDR in cancer cells.

Severe Hyponatremia Associated with the Use of Angiotensin II Receptor Blocker/thiazide Combinations.

There are several widely used combinations of angiotensin II receptor blocker (ARB)/thiazide. The complimentary mechanism of action for such anti-hypertensive therapies is that, while ARB inhibits the vasoconstricting and aldosterone-secreting effects of angiotensin II, hydrochlorothiazide affects the renal tubular mechanisms of electrolyte reabsorption and increases excretion of sodium and chloride in the distal tubule, consequently promoting water excretion. In addition, hypokalemia, which may be triggered by a hydrochlorothiazide-induced increase in urinary potassium loss, is resisted by the use of ARB. Hence, the ARB/thiazide combination is safe in terms of potassium imbalance. For these reasons, fixed-dose ARB/thiazide combination anti-hypertensive drugs have been widely used for the treatment of hypertension. However, there have not been many studies done regarding cases where patients under such regimens showed severe hyponatremia, even when the amount of thiazide included was low. Here we report two cases in which severe hyponatremia occurred following treatment with the ARB/thiazide combinations. Upon discontinuation of the regimen, both patients showed recovery from hyponatremia.

A novel real-time PCR method based on signaling-by-incorporation.

We describe a novel real-time PCR method, which utilizes the in situ generated signal upon incorporation of a fluorogenic nucleotide. The method has been compared with a conventional method and evaluated for practical uses such as quantification of cDNA and malaria diagnosis.