Crystal structure of Helicobacter pylori MinE, a cell division topological specificity factor

In Gram-negative bacteria, proper placement of the FtsZ ring, mediated by nucleoid occlusion and the activities of the dynamic oscillating Min proteins MinC, MinD and MinE, is required for correct positioning of the cell division septum. MinE is a topological specificity factor that counters the activity of MinCD division inhibitor at the mid-cell division site. Its structure consists of an anti-MinCD domain and a topology specificity domain (TSD). Previous NMR analysis of truncated Escherichia coli MinE showed that the TSD domain contains a long α-helix and two anti-parallel β-strands, which mediate formation of a homodimeric α/β structure. Here we report the crystal structure of full-length Helicobacter pylori MinE and redefine its TSD based on that structure. The N-terminal region of the TSD (residues 19–26), previously defined as part of the anti-MinCD domain, forms a β-strand (βA) and participates in TSD folding. In addition, H. pylori MinE forms a dimer through the interaction of anti-parallel βA-strands. Moreover, we observed serial dimer–dimer interactions within the crystal packing, resulting in the formation of a multimeric structure. We therefore redefine the functional domain of MinE and propose that a multimeric filamentous structure is formed through anti-parallel β-strand interactions

Clinical Efficacy of Human Papillomavirus DNA Detection in Urine from Patients with Various Cervical Lesions

A considerable number of adult Korean women avoid a Pap smear due to fear and discomfort of the pelvic examination. A reliable but noninvasive and comfortable screening method would considerably increase the participation rate. To evaluate the clinical efficacy of urine-based human papillomavirus (HPV) detection by oligonucleotide microarray, the results of HPV test from matched cervical swab specimens were compared. HPV DNA was detected in 70 of 100 cervical samples. HPV 16 was the most prevalent type (38/70), followed by types 18, 58, 52, 33, 35, 31, and 51. HPV DNA was identified in 47 of 90 urine samples. HPV 16 was the most prevalent type (30/45), followed by types 18, 52, 35, 51, 58, 33, and 56. The HPV detection rates of the cervical swabs increased in accordance with the severity of the cytologic and histologic diagnosis. The type specific agreement of HPV DNA tests between cervical swabs and urine was good in HPV 16 (kappa index=0.64 [95% CI: 0.50-0.79]), 18, 52, and 58 and fair in HPV 33 and 35. We propose that a urine HPV test is a valuable adjunctive method for a conventional Pap smear and can be used in population screening for cervical cancer in countries where it is difficult to obtain colposcopic specimens for cultural or religious reasons

Randomized Comparison of Four-Times-Daily versus Once-Daily Intravenous Busulfan in Conditioning Therapy for Hematopoietic Cell Transplantation

AbstractSixty patients were randomized to receive intravenous busulfan (iBU) either as 0.8 mg/kg, over 2 hours 4 times a day (BU4 arm) or 3.2 mg/kg, over 3 hours once a day (BU1 arm) in conditioning therapy for hematopoietic cell transplantation. The complete pharmacokinetic parameters for the first busulfan dose were obtained from all patients and were comparable between the 2 arms: for the BU4 and BU1 groups, elimination half-life (mean ± SD) was 2.75 ± 0.22 versus 2.83 ± 0.21 hours, estimated daily AUC was 6058.0 ± 1091.9 versus 6475.5 ± 1099.4 μM·min per day, and clearance was 2.05 ± 0.36 versus 1.91 ± 0.31 mL/min/kg, respectively. Times to engraftment after transplantation were similar between the 2 arms. No significant differences were evident in the occurrence of acute graft-versus-host disease (aGVHD) and hepatic veno-occlusion disease (VOD). Moreover, other toxicities observed within 100 days after transplantation were not significantly different between the 2 arms. The cumulative incidence of nonrelapse mortality was 20.8% in BU4 arm and 13.3% in BU1 arm. In conclusion, our randomized study demonstrates that the pharmacokinetic profiles and posttransplant complications are similar for once-daily iBU and traditional 4-times-daily iBU

A placebo-controlled trial of Korean red ginseng extract for preventing Influenza-like illness in healthy adults

<p>Abstracts</p> <p>Background</p> <p>Standardized Korean red ginseng extract has become the best-selling influenza-like illness (ILI) remedy in Korea, yet much controversy regarding the efficacy of the Korean red ginseng (KRG) in reducing ILI incidence remains. The aim of the study is to assess the efficacy of the KRG extract on the ILI incidence in healthy adults.</p> <p>Methods/Design</p> <p>We will conduct a randomized, double-blind, placebo-controlled study at the onset of the influenza seasons. A total of 100 subjects 30-70 years of age will be recruited from the general populations. The subjects will be instructed to take 9 capsules per day of either the KRG extract or a placebo for a period of 3 months. The primary outcome measure is to assess the frequency of ILI onset in participated subjects. Secondary variable measures will be included severity and duration of ILI symptoms. The ILI symptoms will be scored by subjects using a 4-point scale.</p> <p>Discussion</p> <p>This study is a randomized placebo controlled trial to evaluate the efficacy of the KRG extract compared to placebo and will be provided valuable new information about the clinical and physiological effects of the KRG extract on reduction of ILI incidence including flu and upper respiratory tract infections. The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if KRG extract can be shown to be an effective reduction strategy in ILI incidence.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01478009">NCT01478009</a>.</p

Improvement in the diagnostics of iron deficiency anemia using multiple marker combinations

Anemia of chronic disease (ACD) frequently occurred in patients with chronic inflammatory diseases and can be treated by treating the underlying disease. On the other hand, iron-deficiency anemia (IDA), the most common type of anemia, occurred with iron loss or when the iron requirement of the body was increased. Since the treatment methods for ACD and IDA differ, it is important to clinically distinguish between the two types of anemia. In this study, we investigated and evaluated the performance of a number of biomarkers, including ferritin, soluble transferrin receptor (sTfR), hepcidin, C-reactive protein (CRP) and combination markers containing ferritin for the diagnosis of IDA using serum samples from Korean patients (80 ACD and 48 IDA Korean patients). Among the single markers, ferritin exhibited the best performance with 98.58% AUC and 97.50% sensitivity. In this study, a combination of two biomarkers was used to differentially diagnose IDA and ACD. Among the combination markers, ferritin + sTfR showed the best performance with 99.51% AUC and 98.75% sensitivity. We found that the ferritin + sTfR combination showed the best diagnostic performance with 1.25% higher SN than ferritin alone. Moreover, it also showed 10% better diagnostic performance than the single ferritin marker within the data range where the distinction between ACD and IDA is unclear. We propose that using combination markers containing ferritin may diagnose IDA more accurately and facilitate the determination of the appropriate anemia treatment to expedite patient recovery

Midazolam anesthesia during rigid and flexible cystoscopy

The objective of this study was to investigate the usefulness and safety of midazolam-induced anesthesia for cystoscopy. From September 2005 to March 2006, 80 patients scheduled for regular outpatient follow-up cystoscopy participated in this study. The patients were randomized and classified according to the cystoscope type and midazolam use as follows: group 1 (10 men and 10 women), flexible cystoscopy + midazolam; group 2 (10 men and 10 women), flexible cystoscopy + no midazolam; group 3 (10 men and 10 women), rigid cystoscopy + midazolam; and group 4 (10 men and 10 women), rigid cystoscopy + no midazolam. Immediately after the procedure, the patients were asked to rate their comfort level using a ten-point visual linear analog self-assessment pain scale. The patients assigned in the midazolam group experienced no side-effects from the midazolam. Blood pressure and pulse rate did not change significantly during the procedure. The degree of pain experienced by group 1 was lower than other groups (P < 0.05) and group 4 had a significantly greater pain score than other groups (P < 0.05). No difference was evident between group 2 and 3 regarding the pain score. Midazolam anesthesia may relieve pain during rigid and flexible cystoscopy. Our findings suggest that midazolam anesthesia during cystoscopy is useful and safe