Hb Madrid [beta115(G17)Ala-->Pro] in a Korean family with chronic hemolytic anemia

Hb Madrid, in which the alanine residue at beta115 (G17) is replaced by proline, results in a moderately severe hemolytic anemia due to the disruption of an alpha helical region and the weakening of an alpha1 beta1 contact (1,2). It was first discovered in a single Spanish patient, by protein structural analysis, whose parents did not carry the abnormality (1). The second observation of Hb Madrid was in an American Black teenager by DNA analysis, who had the family history of chronic hemolytic anemia, but none of family members were available for evaluation (3).     

Pulmonary edema after da Vinci-assisted laparoscopic radical prostatectomy: a case report

A 63 year-old man developed sudden pulmonary edema after uneventful robot-assisted laparoscopic radical prostatectomy (RALP) for prostate cancer despite normal preoperative laboratory findings and appropriate anesthetic management. The pulmonary edema was attributed to prolonged (4 hrs) pneumoperitoneum with concomitant high intraabdominal pressure (15-20 mmHg).     

A case of acute appendicitis due to intestinal stricture after intestinal tuberculosis treatment]

Intestinal hemorrhage, perforation, obstruction, and fistula formation are the common complications associated with intestinal tuberculosis. However, these complications usually occur in active stage of intestinal tuberculosis. A 45-year-old man was diagnosed as intestinal tuberculosis and received anti-tuberculosis medications for 9 months. After the end of treatment, intestinal lesion was cured. However a deformed appendiceal orifice due to hypertrophic sear resulting in symptomatic appendicitis was noted. We report a case of acute appendicitis due to intestinal stricture after the successful treatment of intestinal tuberculosis.     

Tubulin Inhibitor Identification by Bioactive Conformation Alignment Pharmacophore‐Guided Virtual Screening

Microtubules are important cellular component that are critical for proper cellular function. Microtubules are synthesized by polymerization of αβ tubulin heterodimers called protofilaments. Microtubule dynamics facilitate proper cell division during mitosis. Disruption of microtubule dynamics by small‐molecule agents inhibits mitosis, resulting in apoptotic cell death and preventing cell cycle progression. To identify a novel small molecule that binds the αβ tubulin interface to affect microtubule dynamics, we developed a bioactive conformation alignment pharmacophore (BCAP) model to screen tubulin inhibitors from a huge database. The application of BCAP model generated based on the known αβ‐tubulin interface binders enabled us to identify several small‐molecules that cause apoptosis in human promyelocytic leukemia (HL‐60) cells. Virtual screening combined with an in vitro assay yielded 15 cytotoxic molecules. In particular, ethyl 2‐(4‐(5‐methyl‐3‐nitro‐1H‐pyrazol‐1‐yl)butanamido)‐4‐phenylthiophene‐3‐carboxylate ( H05 ) inhibited tubulin polymerization with an IC₅₀ of 17.6 μm concentration. The virtual screening results suggest that the application of an unbiased BCAP pharmacophore greatly eliminates unlikely compounds from a huge database and maximizes screening success. From the limited compounds tested in the tubulin polymerization inhibitor (TPI) assay, compound H05 was discovered as a tubulin inhibitor. This compound requires further structure activity optimization to identify additional potent inhibitors from the same class of molecules.     

Pharmacokinetics and Pharmacodynamics of Broccoli Sprouts on the Suppression of Prostate Cancer in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) Mice: Implication of Induction of Nrf2, HO-1 and Apoptosis and the Suppression of Akt-dependent Kinase Pathway

Purpose  

In the present study, we have evaluated the pharmacokinetics and the in vivo prostate chemopreventive activity of broccoli sprouts.     

Combined transcatheter arterial chemoembolization and local radiotherapy of unresectable hepatocellular carcinoma

PURPOSE: The best prognosis in hepatocellular carcinoma (HCC) can be achieved with surgical resection; however, the number of resected cases are limited due to advanced lesions or associated liver disease. The purpose of this study was to investigate the efficacy and toxicity of a prospective trial of combined transcatheter arterial chemoembolization (TACE) and local radiotherapy (RT) in unresectable HCC. METHODS AND MATERIALS: Patients with histologically proven unresectable HCC due to either advanced lesions or associated cirrhosis were eligible. From March 1992 to August 1994, 30 patients were entered into this study. TACE was performed with Lipiodol (5 ml) and doxorubicin (Adriamycin ; 50 mg), followed by gelatin sponge particle (Gelfoam) embolization. Local RT was started within 7-10 days following TACE. Mean tumor dose was 44.0+/-9.3 Gy in daily 1.8 Gy fractions. Response was assessed by computerized tomography (CT) scan 4-6 weeks following completion of the treatment and then at 1-3-month intervals. Survival was calculated from the start of TACE using the Kaplan-Meier method. RESULTS: An objective response was observed in 19 patients, giving a response rate of 63.3%. Distant metastasis occurred in 10 patients, with 8 in the lung only and 2 in both lung and bone. Survival rates at 1, 2, and 3 years were 67%, 33.3%, and 22.2%, respectively. Median survival was 17 months. There were 6 patients surviving more than 3 years. Toxicity included transient elevation of liver function tests in all patients, fever in 20, thrombocytopenia in 4, and nausea and vomiting in 1. There was no treatment-related death. CONCLUSION: Combined TACE and local RT is feasible and tolerable. It gives a 63.3% response rate with median survival of 17 months. We feel that this regimen would be a new promising modality in unresectable HCC. Further study is required to compare the therapeutic efficacy of this regimen to TACE alone.     

SYNCRIP (synaptotagmin-binding, cytoplasmic RNA-interacting protein) is a host factor involved in hepatitis C virus RNA replication

Hepatitis C virus (HCV) RNA replication requires viral nonstructural proteins as well as cellular factors. Recently, a cellular protein, synaptotagmin-binding, cytoplasmic RNA-interacting protein (SYNCRIP), also known as NSAP1, was found to bind HCV RNA and enhance HCV IRES-dependent translation. We investigate whether this protein is also involved in the HCV RNA replication. We found that SYNCRIP was associated with detergent-resistant membrane fractions and colocalized with newly-synthesized HCV RNA. Knock-down of SYNCRIP by siRNA significantly decreased the amount of HCV RNA in the cells containing a subgenomic replicon or a full-length viral RNA. Lastly, an in vitro replication assay after immunodepletion of SYNCRIP showed that SYNCRIP was directly involved in HCV RNA replication. These findings indicate that SYNCRIP has dual functions, participating in both RNA replication and translation in HCV life cycle.