Deregulation of HDAC5 by Viral Interferon Regulatory Factor 3 Plays an Essential Role in Kaposi's Sarcoma-Associated Herpesvirus-Induced Lymphangiogenesis.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi's sarcoma (KS), which is one of the most common HIV-associated neoplasms. The endothelium is the thin layer of squamous cells where vascular blood endothelial cells (BECs) line the interior surface of blood vessels and lymphatic endothelial cells (LECs) are in direct contact with lymphatic vessels. The KS lesions contain a prominent compartment of neoplastic spindle morphology cells that are closely related to LECs. Furthermore, while KSHV can infect both LECs and BECs in vitro, its infection activates genetic programming related to lymphatic endothelial cell fate, suggesting that lymphangiogenic pathways are involved in KSHV infection and malignancy. Here, we report for the first time that viral interferon regulatory factor 3 (vIRF3) is readily detected in over 40% of KS lesions and that vIRF3 functions as a proangiogenic factor, inducing hypersprouting formation and abnormal growth in a LEC-specific manner. Mass spectrometry analysis revealed that vIRF3 interacted with histone deacetylase 5 (HDAC5), which is a signal-responsive regulator for vascular homeostasis. This interaction blocked the phosphorylation-dependent cytosolic translocation of HDAC5 and ultimately altered global gene expression in LECs but not in BECs. Consequently, vIRF3 robustly induced spindle morphology and hypersprouting formation of LECs but not BECs. Finally, KSHV infection led to the hypersprouting formation of LECs, whereas infection with a ΔvIRF3 mutant did not do so. Collectively, our data indicate that vIRF3 alters global gene expression and induces a hypersprouting formation in an HDAC5-binding-dependent and LEC-specific manner, ultimately contributing to KSHV-associated pathogenesis.IMPORTANCE Several lines of evidences indicate that KSHV infection of LECs induces pathological lymphangiogenesis and that the results resemble KS-like spindle morphology. However, the underlying molecular mechanism remains unclear. Here, we demonstrated that KSHV vIRF3 is readily detected in over 40% of various KS lesions and functions as a potent prolymphangiogenic factor by blocking the phosphorylation-dependent cytosolic translocation of HDAC5, which in turn modulates global gene expression in LECs. Consequently, vIRF3-HDAC5 interaction contributes to virus-induced lymphangiogenesis. The results of this study suggest that KSHV vIRF3 plays a crucial role in KSHV-induced malignancy

Bare-metal stents versus drug-eluting stents in large (≥3.5mm) single coronary artery: Angiographic and clinical outcomes at 6 months

SummaryBackgroundAlthough drug-eluting stents (DES) have been shown to dramatically reduce restenosis and improve the rate of event-free survival in large randomized trials, the benefit of DES appears to be limited to restenosis. In large arteries, it is not clear which type of stent is more superior in angiographic and clinical outcomes between DES and bare-metal stents (BMS). We compared the angiographic and clinical outcomes of DES versus BMS in large arteries (≥3.5mm).MethodTwo hundred and forty patients from March 2002 to March 2007 received stents; 196 patients were treated with DES (44.9% sirolimus-eluting stents; 43.9% paclitaxel-eluting stents; 11.2% zotarolimus-eluting stents) and 44 with cobalt–chromium BMS for single de novo lesions in a large vessel. All subjects received aspirin, clopidogrel, and/or cilostazol as the standard antiplatelet regimen. The angiographic and clinical outcomes were evaluated at 6 months.ResultsFor the baseline characteristics, there were no significant differences between the DES and BMS groups. In addition, for the initially implanted stent there was no difference in the length, stent diameter, and lesion site between the two groups. After 6 months, the follow-up angiogram showed that in-stent diameter restenosis and late loss was more common with BMS than DES (39±21% vs. 19±17%, p=0.007; 1.44±0.83mm vs. 0.62±0.58mm, p=0.009, respectively). However, the target-lesion revascularization/target-vessel revascularization, and total major adverse cardiac events showed no significant differences between the groups (5.3% vs. 3.6%, p=0.62; 5.3% vs. 4.6%, p=0.86, respectively).ConclusionThe DES and cobalt–chromium BMS placed in large coronary arteries showed equally favorable 6-month clinical outcomes, although the 6-month angiographic results appeared more favorable in the DES group than in the BMS group

A Family of H723R Mutation for SLC26A4 Associated with Enlarged Vestibular Aqueduct Syndrome

Recessive mutations of the SLC26A4 (PDS) gene on chromosome 7q31 can cause sensorineural deafness with goiter (Pendred syndrome, OMIM 274600) or NSRD with goiter (at the DFNB4 locus, OMIM 600791). H723R (2168A>G) is the most commonly reported SLC26A4 mutations in Korean and Japanese and known as founder mutation. We recently experienced one patient with enlarged vestibular aqueduct syndrome. The genetic study showed H723R homozygous in the proband and H723R heterozygous mutation in his family members. The identification of a disease-causing mutation can be used to establish a genotypic diagnosis and provide important information to both families and their physicians

Laparoscopic Myomectomy for Large Myomas

The aim of this study was to assess the feasibility and efficacy of laparoscopic myomectomy (LM) for large myomas. A subpopulation of 51 patients with myomas 8 cm or larger in diameter was selected from 155 patients who underwent LM at Kangbuk Samsung Hospital from July 2003 to November 2006. The mean age of the patients was 34.9±5.6 yr, mean parity was 0.6±0.9, and 8 patients had a previous operative history. The most common operative indication was a palpable abdominal mass (24 patients, 47%). The mean operating time was 85.6±38.9 min, and the mean diameter of the largest myoma was 9.3±1.8 cm. The mean change in hemoglobin concentration was 2.1±1.2 g/dL. Histopathological diagnosis included 49 patients of leiomyoma (96.1%) and 2 patients of leiomyoma with adenomyosis (3.9%). Postoperatively, a transfusion was done in 7 patients, and a case of subcutaneous emphysema was noted. None of the operations was switched to laparotomy. With the newly-developed screw and the port placement system that was modified from the Choi's 4-trocar method to obtain better surgical vision, LM of large myomas proved to be one of the efficient and feasible methods

Titanium dioxide nanoparticles oral exposure to pregnant rats and its distribution

Background: Titanium dioxide (TiO2) nanoparticles are among the most manufactured nanomaterials in the industry, and are used in food products, toothpastes, cosmetics and paints. Pregnant women as well as their conceptuses may be exposed to TiO2 nanoparticles; however, the potential effects of these nanoparticles during pregnancy are controversial, and their internal distribution has not been investigated. Therefore, in this study, we investigated the potential effects of oral exposure to TiO2 nanoparticles and their distribution during pregnancy. TiO2 nanoparticles were orally administered to pregnant Sprague-Dawley rats (12 females per group) from gestation days (GDs) 6 to 19 at dosage levels of 0, 100, 300 and 1000 mg/kg/day, and then cesarean sections were conducted on GD 20. Results: In the maternal and embryo-fetal examinations, there were no marked toxicities in terms of general clinical signs, body weight, food consumption, organ weights, macroscopic findings, cesarean section parameters and fetal morphological examinations. In the distribution analysis, titanium contents were increased in the maternal liver, maternal brain and placenta after exposure to high doses of TiO2 nanoparticles. Conclusion: Oral exposure to TiO2 during pregnancy increased the titanium concentrations in the maternal liver, maternal brain and placenta, but these levels did not induce marked toxicities in maternal animals or affect embryo-fetal development. These results could be used to evaluate the human risk assessment of TiO2 nanoparticle oral exposure during pregnancy, and additional comprehensive toxicity studies are deemed necessary considering the possibility of complex exposure scenarios and the various sizes of TiO2 nanoparticles

Hemolytic Disease of the Newborn Associated with Anti-Jr(a) Alloimmunization in a Twin Pregnancy: The First Case Report in Korea

Jr(a) is a high-frequency antigen found in all ethnic groups. However, the clinical significance of the anti-Jr(a) antibody has remained controversial. Most studies have reported mild hemolytic disease of the newborn and fetus (HDNF) in Jr(a)-positive patients. Recently, fatal cases of HDNF have also been reported. We report the first case of HDNF caused by anti-Jr(a) alloimmunization in twins in Korea. A 33-yr-old nulliparous woman with no history of transfusion or amniocentesis was admitted at the 32nd week of gestation because of vaginal bleeding caused by placenta previa. Anti-Jr(a) antibodies were detected in a routine laboratory examination. An emergency cesarean section was performed at the 34th week of gestation, and 2 premature infant twins were delivered. Laboratory examination showed positive direct antiglobulin test and Jr(a+) phenotype in the red blood cells and the presence of anti-Jr(a) antibodies in the serum in both neonates. The infants underwent phototherapy for neonatal jaundice; this was followed by conservative management. They showed no further complications and were discharged on the 19th postpartum day. Preparative management to ensure the availability of Jr(a-) blood, via autologous donation, and close fetal monitoring must be performed even in cases of first pregnancy in Jr(a-) women. (Korean J Lab Med 2010;30:511-5)Arriaga F, 2009, TRANSFUSION, V49, P813, DOI 10.1111/j.1537-2995.2009.02118.xPeyrard T, 2008, TRANSFUSION, V48, P1906, DOI 10.1111/j.1537-2995.2008.01787.xROBACK JD, 2008, TECHNICAL MANUAL, P411CHUNG HJ, 2007, KOREAN J BLOOD TRANS, V18, P111Ishihara Y, 2006, FETAL DIAGN THER, V21, P269, DOI 10.1159/000091354Daniels GL, 2004, VOX SANG, V87, P304Kwon MY, 2004, TRANSFUSION, V44, P197Bellver-Pradas J, 2001, AM J OBSTET GYNECOL, V184, P75STROUP M, 1970, P 23 ANN M AM ASS BL, P86KIM DW, 1995, ELS APPL ELECT MAT, V6, P185MIYAZAKI T, 1994, VOX SANG, V66, P51OGASAWARA K, 1990, ACTA HAEMATOL JAPON, V53, P1131GARRATTY G, 1990, TRANSFUS MED REV, V4, P297NANCE SJ, 1987, TRANSFUSION, V27, P449BACON J, 1986, TRANSFUSION, V26, P543LEVENE C, 1986, TRANSFUSION, V26, P119TAKABAYASHI T, 1985, TOHOKU J EXP MED, V145, P97TOY P, 1981, VOX SANG, V41, P40ORRICK LR, 1980, AM J OBSTET GYNECOL, V137, P135NAKAJIMA H, 1978, VOX SANG, V35, P265VEDO M, 1978, TRANSFUSION, V18, P569TRITCHLER JE, 1977, TRANSFUSION, V17, P177KENDALL AG, 1976, TRANSFUSION, V16, P646

Novel epitheliomesenchymal biphasic stomach tumour (gastroblastoma) in a 9-year-old: morphological, usltrastructural and immunohistochemical findings

Gastroblastoma is a rare gastric epitheliomesenchymal biphasic tumour composed of spindle and epithelial cells, reported by Miettinen et al in a series of three cases in 2009. All those cases arose in stomachs of young adults. Neither the epithelial nor the mesenchymal component displayed sufficient atypia to diagnose a carcinosarcoma or other malignancy. On immunohistochemistry, the epithelial component expressed cytokeratin, and the mesenchymal component was positive for vimentin and CD10. Miettinen et al designated these neoplasms as gastroblastomas based on their similarities with other childhood blastomas such as pleuropulmonary blastoma and nephroblastoma. This report describes a probable fourth case of this unique type of neoplasm. The present case arose in the gastric antrum of a 9-year-old boy. While similarities were evident with the other cases, there were some differences. The epithelial component was more predominant and showed more mature morphology. Immunohistochemically, the epithelial component showed immunolabelling for c-KIT and CD56. The mesenchymal component was only focally positive for CD10. Ultrastructually, desmosomes and microvilli were found supporting a truly epithelial lesion