High-resolution analysis of condition-specific regulatory modules in Saccharomyces cerevisiae

A novel approach for identifying condition-specific regulatory modules in yeast reveals functionally distinct coregulated submodules

Clinical and Pathological Characteristics of Four Korean Patients with Limb-Girdle Muscular Dystrophy type 2B

Limb-girdle muscular dystrophy type 2B (LGMD2B), a subtype of autosomal recessive limb-girdle muscular dystrophy (ARLGMD), is characterized by a relatively late onset and slow progressive course. LGMD2B is known to be caused by the loss of the dysferlin protein at sarcolemma in muscle fibers. In this study, the clinical and pathological characteristics of Korean LGMD2B patients were investigated. Seventeen patients with ARLGMD underwent muscle biopsy and the histochemical examination was performed. For the immunocytochemistry, a set of antibodies against dystrophin, α, β, γ, δ-sarcoglycans, dysferlin, caveolin-3, and β-dystroglycan was used. Four patients (24%) showed selective loss of immunoreactivity against dysferlin at the sarcolemma on the muscle specimens. Therefore, they were classified into the LGMD2B category. The age at the onset of disease ranged from 9 yr to 33 yr, and none of the patients was wheelchair bound at the neurological examination. The serum creatine kinase (CK) was high in all the patients (4010-5310 IU/L). The pathologic examination showed mild to moderate dystrophic features. These are the first Korean LGMD2B cases with a dysferlin deficiency confirmed by immunocytochemistry. The clinical, pathological, and immunocytochemical findings of the patients with LGMD2B in this study were in accordance with those of other previous reports

Primary Malignant Pericardial Mesothelioma Presenting as Acute Pericarditis

We report on a 21-year-old man with fever, dyspnea, and pleuritic chest pain. An electrocardiography showed ST elevation in multiple lead and thoracic echocardiography revealed moderate pericardial effusion. He was initially diagnosed with acute pericarditis, and treated with nonsteroidal anti-inflammatory drugs and colchicines with clinical and laboratory improvement. After 1 month of medication, his symptoms recurred. An echocardiography showed constrictive physiology and the patient was treated with steroid on the top of current medication. The patient had been well for 7 months until dyspnea and edema developed, when an echocardiography showed marked increased pericardial thickness and constriction. Pericardial biopsy was performed and primary malignant pericardial mesothelioma was diagnosed. Malignancy should be considered in the differential diagnosis of recurrent pericarditis

Selective Uterine Artery Embolization for Management of Interstitial Ectopic Pregnancy

Interstitial ectopic pregnancy is a rare condition of pregnancy and may be very dangerous if not identified and treated urgently. We report a case of successful treatment of an interstitial pregnancy using selective uterine artery embolization. A 27-year-old woman with interstitial pregnancy was treated by uterine artery embolization after failure of systemic methotrexate treatment. Her serum beta-human chorionic gonadotropin (β-hCG) was undetectable one month after the therapeutic embolization and transvaginal sonography 31 days after embolization showed normal endometrium and cornu. The patient achieved a normal pregnancy eight months after embolization

Hepatocyte growth factor suppresses vascular endothelial growth factor-induced expression of endothelial ICAM-1 and VCAM-1 by inhibiting the nuclear factor-kappaB pathway

Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are potent angiogenic factors that have been used clinically to induce angiogenesis. However, concerns have been raised about VEGF because of its proinflammatory actions, which include enhancing the adhesion of leukocytes to endothelial cells. We have examined the possible antiinflammatory effects of HGF on the vasculature. HGF, unlike VEGF, did not alter leukocyte adhesion to endothelial cells. Instead it inhibited VEGF-induced leukocyte-endothelial cell interactions and the endothelial expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). In a skin inflammation model, VEGF-treated mice showed a significant increase of leukocytes infiltrated or adherent to the luminal surface of blood vessels, as compared with vehicle- or HGF-treated mice. The VEGF effect was markedly suppressed by coadministration of HGF. RT-PCR and promoter analysis revealed that HGF downregulated VEGF-mediated expression of ICAM-1 and VCAM-1 at the transcriptional level. Furthermore, these inhibitory effects coincided with suppression of IkappaB kinase activity, and this in turn prevented the activation of the inflammatory transcription factor NF-kappaB. Taken together, our results demonstrate that HGF suppresses VEGF-induced inflammation presumably by inhibiting the endothelial NF-kappaB pathway. This suggests that combined treatment with HGF and VEGF could be superior to treatment with either factor alone for enhancing therapeutic angiogenesis while avoiding inflammation

Immunotherapy of Malignant Melanoma with Tumor Lysate-Pulsed Autologous Monocyte-Derived Dendritic Cells

PURPOSE: Dendritic cell (DC) vaccination for melanoma was introduced because melanoma carries distinct tumor-associated antigens. The purpose of this study was to investigate the efficacy and safety of DC vaccination for melanoma in Korea. MATERIALS AND METHODS: Five patients with stage IV and one with stage II were enrolled. Autologous monocyte-derived DCs (MoDCs) were cultured and pulsed with tumor-lysate, keyhole limpet hemocyanin, and cytokine cocktail for mature antigen-loaded DC. DC vaccination was repeated four times at 2-week intervals and 2-4×10⁷ DC were injected each time. RESULTS: Reduced tumor volume was observed by PET-CT in three patients after DC vaccination. Delayed type hypersensitivity responses against tumor antigen were induced in five patients. Tumor antigen-specific IFN-γ-producing peripheral blood mononuclear cells were detected with enzyme-linked immunosorbent spot in two patients. However, the overall clinical outcome showed disease progression in all patients. CONCLUSION: In this study, DC vaccination using tumor antigen-loaded, mature MoDCs led to tumor regression in individual melanoma patients. Further standardization of DC vaccination protocol is required to determine which parameters lead to better anti-tumor responses and clinical outcomes.ope