Epigenetic regulation of Kcna3-encoding Kv1.3 potassium channel by cereblon contributes to regulation of CD4+ T-cell activation.

The role of cereblon (CRBN) in T cells is not well understood. We generated mice with a deletion in Crbn and found cereblon to be an important antagonist of T-cell activation. In mice lacking CRBN, CD4(+) T cells show increased activation and IL-2 production on T-cell receptor stimulation, ultimately resulting in increased potassium flux and calcium-mediated signaling. CRBN restricts T-cell activation via epigenetic modification of Kcna3, which encodes the Kv1.3 potassium channel required for robust calcium influx in T cells. CRBN binds directly to conserved DNA elements adjacent to Kcna3 via a previously uncharacterized DNA-binding motif. Consequently, in the absence of CRBN, the expression of Kv1.3 is derepressed, resulting in increased Kv1.3 expression, potassium flux, and CD4(+) T-cell hyperactivation. In addition, experimental autoimmune encephalomyelitis in T-cell-specific Crbn-deficient mice was exacerbated by increased T-cell activation via Kv1.3. Thus, CRBN limits CD4(+) T-cell activation via epigenetic regulation of Kv1.3 expression.

Supratentorial extraventricular anaplastic ependymoma presenting with repeated intratumoral hemorrhage.

Supratentorial extraventricular anaplastic ependymomas are extremely rare. We report the case of a 23-year-old male with a supratentorial extraventricular anaplastic ependymoma that presented with repeated intratumoral hemorrhage. The patient was diagnosed with an intracerebral hematoma in the left occipital lobe and underwent operation. The hematoma did not reveal tumor cells, but a new tumor grew in the same location 5 years later. Magnetic resonance imaging showed a tumor with intratumoral hemorrhage. The patient underwent the tumor resection. Intraoperative findings showed that the tumor had no continuity with the ventricle. Histopathological examinations confirmed an anaplastic ependymoma. The spinal evaluation was unremarkable, and radiotherapy was administered to the left occipital lobe. Four years later, the tumor recurred at the cervicomedullary junction and T8-T9 levels. This case demonstrates that anaplastic ependymomas should be included in the differential diagnoses of supratentorial extraventricular tumors presenting with repeated intratumoral hemorrhage.

Risk factors and incidence for peripheral arterial disease in patients with typical lumbar spinal stenosis.

OBJECTIVE: Intermittent claudication (IC) is a typical symptom of peripheral arterial disease (PAD) and lumbar spinal stenosis (LSS). In order to prevent misdiagnosis of vascular disease, it is important to know the incidence of and risk factors for PAD in patients with LSS. Therefore, the aim of our study was to evaluate the incidence of and risk factors for PAD in patients with typical and severe LSS who underwent spinal surgical treatment. METHODS: The occurrence of PAD was examined retrospectively in 171 consecutive patients with LSS and severe IC who underwent surgical treatment at our hospital from June 2012 to June 2013. Data were collected on background characteristics (sex, age) and known risk factors for PAD, such as hypertension, diabetes mellitus, smoking, hyperlipidemia, stroke, and ischemic heart disease. RESULTS: Of the 171 patients enrolled, 7 had an abnormal ankle-brachial index (ABI). Computed tomography angiography (CTA) was performed in these patients, and a final diagnosis of PAD was established for all 7 patients. The incidence of PAD in all patients with LSS was 4.1%(7 of 171). Stroke and ischemic heart disease were significantly more common in the LSSPAD group compared with the LSS group. Multiple logistic regression analyses with a forced-entry method revealed that age and stroke (p<0.05) were independent risk factors for PAD. CONCLUSION: To prevent misdiagnosis of fatal PAD, we recommend ABI be assessed in patients with LSS and history of stroke.

Peroxisome-localized hepatitis Bx protein increases the invasion property of hepatocellular carcinoma cells.

HBx acts as a multifunctional regulator that modulates various cellular responses, which can lead to development and progression of hepatocellular carcinoma (HCC). Here, we show that the HBx protein is also localized to peroxisomes, and this increases cellular reactive oxygen species (ROS) to levels that are higher than when HBx is localized to other organelles. The elevated ROS strongly activated nuclear factor (NF)-κB. In addition, the peroxisome-localized HBx increased the expressions of matrix metalloproteinases and decreased the expression of E-cadherin, which increased the invasive ability of HCC cells. Thus, a specific distribution of HBx to peroxisomes may contribute to HCC progression by increasing the invasive ability of HCC cells through elevation of the cellular ROS level.

Different binding mechanisms in biosorption of reactive dyes according to their reactivity.

Various binding mechanisms for the uptake of reactive dyes by the protonated waste biomass of Corynebacterium glutamicum were investigated. As model reactive dyes, Reactive Blue 4 (RB 4), Reactive Orange 16 (RO 16) and Reactive Yellow 2 (RY 2) were used in this study. The solution pH strongly influenced the sorption capacity and the binding mechanisms of reactive dyes by C. glutamicum. At acidic pH, the electrostatic interaction was found to be a major binding mechanism. The maximum uptakes of RY 2, RO 16 and RB 4 at pH 2 were estimated to be 155.0+/-14.1, 156.6+/-6.7 and 184.9+/-16.4mg/g, respectively. Under alkaline conditions, the binding mechanisms were quite different according to the reactivity of reactive dyes. It was found that chemical bonding existed between the biomass surface and dye molecules under basic pH conditions.

Biosorption of reactive black 5 by Corynebacterium glutamicum biomass immobilized in alginate and polysulfone matrices.

Corynebacterium glutamicum, a lysine fermentation industry waste, showed promise for the removal of Reactive black 5 (RB5). Due to practical difficulties in solid-liquid separation, the free biomass was immobilized in two polymer matrices: calcium alginate and polysulfone. Initially, the optimization of biomass loading in polymeric beads and bead dosage were examined. Of the different combinations examined, 4% (with bead dosage of 2 g per 40 ml) and 14% (with bead dosage of 1 g per 40 ml) in the case of alginate and polysulfone beads, respectively, were identified as the optimal conditions. According to the Langmuir model, at pH 1, the maximum RB5 uptakes of 352, 282 and 291 mg g(-1) were observed for free, alginate and polysulfone-immobilized biomass, respectively. According to the Weber-Morris model, intraparticle diffusion was found to be the potential rate limiting step for the immobilized beads. Regeneration experiments, with 0.01 M NaOH and Na(2)CO(3) as eluents, revealed that polysulfone beads exhibited invariable RB5 uptake capacity and very high mechanical stability even at the end of twentieth cycle, confirming the technical feasibility of the biosorption process for industrial applications.

[Two cases of natural human infection by Echinostoma hortense and its second intermediate host in Wonju area]

Two cases of human Echinostoma hortense infection and their probable infection source were identified by praziqantel (Distocide) treatment of the patients and by examining two kinds of fresh water fish which were eaten raw by them. The result of the research can be summarized as follows: The patients, each aged 31 and 30, were residing in the same house in Wonju City, Kangwon Province. The first case was hospitalized due to epidemic hemorrhagic fever (E.H. fever) and the second case was healthy but had slight degree of abdominal pain and diarrhea from time to time. In the stool examination, eggs of E. hortense (114.3 x 71.0 micrometer average from the first case and 119.1 x 68.3 micrometer average from the second) were found. By administering single dose of praziquantel (10~15 mg/kg) and purgation with magnesium salt to them, six adults of E. hortense were collected from the diarrheal stools of the second case. By examining 84 Moroco oxycephalus and 20 Carassius carassius which were captured at the place where the two patients had captured and eaten the fresh water fish, the metacercariae of Echinostoma sp. were found from 3 (3.5 percent) M. oxycephalus. After the experimental infection of 3 isolated metacercariae to one albino rat three adults of E. hortense were recovered. By the present study, the two patients revealing the echinostomatid eggs in their stools were proven to be infected with E. hortense and to be the second and third human cases of this fluke infection in Korea. Moroco oxycephalus harboured the metacercariae of E. hortense and appeared to be a new second intermediate host.