Selective activation of adrenergic β1 receptors induces heme oxygenase 1 production in RAW264.7 cells

AbstractWe hypothesized that catecholamines through β-adrenoceptor might modulate macrophage function. We showed that isoproterenol concentration-dependently induced HO-1 production through β1-but not β2-adrenoceptor. Production was increased by forskolin and inhibited by pretreatment with the PKA inhibitor, H-89. Furthermore, induction of HO-1 by isoproterenol effectively protected RAW264.7 cells from effects of glucose oxidase treatment, which was abrogated either by HO-1 inhibitor, ZnPP IX and β-adenoceptor antagonist, propranolol. Thus, stimulation of HO-1 production through β1-adenoceptors, and via the PKA pathways by isoproterenol, can enable RAW264.7 cells to resist oxidant stress, suggesting that catecholamine hormones may be necessary, at least, to maximize defending role of macrophages

Isolated primary schwannoma arising on the colon: report of two cases and review of the literature

Primary schwannoma of the large intestine is an extremely rare neoplasm. Here, we report two cases of colonic schwannoma confirmed pathologically after laparoscopic resection. A 52-year-old female and a 59-year-old female were referred by their general practitioners to our coloproctologic clinic for further evaluation and management of colonic submucosal masses. Colonoscopies performed in our institution revealed round submucosal tumors with a smooth and intact mucosa in the mid-ascending and descending colon, respectively. Computed tomography (CT) scans showed an enhancing soft tissue mass measuring 2 × 2 cm in the right colon and well-defined soft tissue nodule measuring 1.5 × 1.7 cm in the proximal descending colon, respectively. We performed laparoscopic right hemicolectomy and segmental left colectomy under the preoperative impression of gastrointestinal stromal tumors. Two cases were both diagnosed to be benign schwannoma of the colon after immunohistochemical stains (S-100 (+), smooth muscle actin (-), CD117 (-), and CD34 (-))

Immuno-chromatographic Analysis for HPV-16 and 18 E7 Proteins as a Biomarker of Cervical Cancer Caused by Human Papillomavirus

Among the more than 120 different types of human papillomavirus (HPV), types 16 and 18 have been known to be high risk agents that cause cervical cancer. We examined, in an immuno-chromatographic analysis, the potential of using the early gene product. E7 protein, as a diagnostic marker of cervical cancer caused by HPV. We developed monoclonal antibodies specific to HPV-16 and 18 E7 proteins that were produced from bacterial cells using, gene recombinant technology. For each E7 protein, the optimal antibody pair was selected using the immuno-chromatographic sandwich-type binding system based on the lateral flow through membrane pores. Under these conditions, this rapid testing assay had a detection capability as low as 2 ng/mL of E7 protein. Furthermore, since viral analysis required the host cell to be lysed using chemicals such as detergents, it was possible that the E7 protein was structurally damaged during this process, which would result in a decrease in detection sensitivity. Therefore, we examined the detrimental effects caused by different detergents on the E7 protein using HeLa cells as the host. In these experiments, we found that the damage caused by the detergent, nonylphenylpolyethylene glycol (NP-40), was minimal relative to Triton X-100 commonly used or the cell lysis. Temperature also affected the stability oldie E7 protein, and we found that the E7 protein was stabilized at 4 T. for about 2 h, which was 4 times longer than at room temperature. Finally, a HPV-infected cervical cancer cell line, which was used as a real sample model, was treated using the optimized conditions and the presence of E7 proteins were analyzed by immuno-chromatography. The results of this experiment demonstrated that this rapid test could specifically detect HPV-infected samples.Cho IH, 2009, ANAL CHIM ACTA, V632, P247, DOI 10.1016/j.aca.2008.11.019Liang YJ, 2008, INT J BIOCHEM CELL B, V40, P2431, DOI 10.1016/j.biocel.2008.04.003Ressler S, 2007, CLIN CANCER RES, V13, P7067, DOI 10.1158/1078-0432.CCR-07-1222Jeon JH, 2007, EXP MOL MED, V39, P621Mirecka EA, 2006, PROTEIN EXPRES PURIF, V48, P281, DOI 10.1016/j.pep.2006.04.017Nishimura A, 2006, MICROBES INFECT, V8, P984, DOI 10.1016/j.micinf.2005.10.015Cho JH, 2006, ANAL CHEM, V78, P793, DOI 10.1021/ac051453vHuh KW, 2005, P NATL ACAD SCI USA, V102, P11492, DOI 10.1073/pnas.0505337102Ono T, 2003, J IMMUNOL METHODS, V272, P211DeFilippis RA, 2003, J VIROL, V77, P1551, DOI 10.1128/JVI.77.2.1551-1563.2003Jeon JH, 2002, EXP MOL MED, V34, P496VINCE A, 2002, J CLIN VIROL, V25, P109Chen XJS, 2001, J MOL BIOL, V307, P173Paek SH, 2000, METHODS, V22, P53, DOI 10.1006/meth.2000.1036Walboomers JMM, 1999, J PATHOL, V189, P12Wertlake P, 1999, J REPROD MED, V44, P11JEON S, 1995, P NATL ACAD SCI USA, V92, P1654WILBUR DC, 1994, AM J CLIN PATHOL, V101, P209SCHEFFNER M, 1993, CELL, V75, P495SELVEY LA, 1992, J VIROL METHODS, V37, P119MAY K, 1991, AM J OBSTET GYNECOL, V165, P2000DYSON N, 1989, SCIENCE, V243, P934NELSON PH, 1989, EMBO J, V8, P3905GISSMANN L, 1986, VIRAL ETIOLOGY CERVI, P217CHANG JY, 1985, EUR J BIOCHEM, V151, P217

Preoperative Magnetic Resonance Imaging Evaluation in Patients with Adolescent Idiopathic Scoliosis

Study DesignRetrospective case series.PurposeThe purpose of this study was to examine the incidence of neural axis abnormalities and the relevant risk factors in patients with adolescent idiopathic scoliosis (AIS).Overview of LiteratureThe use of preoperative magnetic resonance imaging (MRI) to assess the whole spine in patients with idiopathic scoliosis is controversial, and indications for such MRI evaluations have not been definitively established. However, we routinely use whole-spine MRI in patients with scoliosis who are scheduled to undergo surgical correction.MethodsA total of 378 consecutive patients with presumed AIS who were admitted for spinal surgery were examined for neural axis abnormalities using MRI. To differentiate patients with normal and abnormal MRI findings, the following clinical parameters were evaluated: age, sex, menarcheal status, rotation angle (using a scoliometer), coronal balance, shoulder height difference, and low back pain. We radiographically evaluated curve type, thoracic or thoracolumbar curve direction, curve magnitude and flexibility, apical vertebral rotation, curve length, coronal balance, sagittal balance, shoulder height difference, thoracic kyphosis, and the Risser sign.ResultsNeural axis abnormalities were detected in 24 patients (6.3%). Abnormal MRI findings were significantly more common in males than in females and were associated with increased thoracic kyphosis. However, there were no significant differences in terms of the other measured parameters.ConclusionsAmong the patients with presumed AIS who received preoperative whole-spine MRI, 6.3% had neural axis abnormalities. Males and patients with increased thoracic kyphosis were at a higher risk

Design of Selective Gas Sensors Using Additive-Loaded In2O3 Hollow Spheres Prepared by Combinatorial Hydrothermal Reactions

A combinatorial hydrothermal reaction has been used to prepare pure and additive (Sb, Cu, Nb, Pd, and Ni)-loaded In2O3 hollow spheres for gas sensor applications. The operation of Pd- and Cu-loaded In2O3 sensors at 371 °C leads to selective H2S detection. Selective detection of CO and NH3 was achieved by the Ni-In2O3 sensor at sensing temperatures of 371 and 440 °C, respectively. The gas responses of six different sensors to NH3, H2S, H2, CO and CH4 produced unique gas sensing patterns that can be used for the artificial recognition of these gases

Reversible Sensorineural Hearing Loss due to Pachymeningitis Associated with Elevated Serum MPO-ANCA

Hypertrophic pachymeningitis is a progressive disease resulting in a diffuse thickening of dura mater due to inflammation, tumor or autoimmune diseases, but most cases are idiopathic. It is seldom reported to be related to sensorineural hearing loss, but it can cause sensorineural hearing loss which can be potentially reversed through treatment. Here, we report the case of a 54-year-old woman who had progressive, bilateral, worse in the left, sensorineural hearing loss and visual disturbance with an accompanying headache over several months. Brain MRI showed diffusely thickened dura mater, highly enhanced after gadolinium administration, which was consistent with pachymeningitis. It was assumed to be related to autoimmune pathogenesis on the basis of elevated serum myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) titers. After empirical steroid and cyclophosphamide therapy, auditory impairment improved, especially in the high frequency region of the pure tone audiogram, and significant improvement in the word recognition test. Moreover, a follow-up MRI revealed much decreased enhancement of the dura mater, and the MPO-ANCA titer decreased to within the normal range. In the case of rapidly progressive sensorineural hearing loss or hearing impairment accompanying other cranial neuropathy, pachymeningitis should be taken into consideration, and brain MRI with gadolinium enhancement is the best method of detecting it. Also, to ensure proper treatment, a cautious evaluation including an ANCA work-up should be performed

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Methods/Design Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. Discussion This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. Trial registration ClinicalTrials.gov Identifier NCT0158936

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

This study is being supported by grant no 04-2012-0290 from the SNUH Research fund and by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIP)(No. 2013005540). Letrozole and metformin are being supplied by the pharmaceutical company, Shin Poong Pharm. Co., Ltd.Background : Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Methods/Design : Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. Discussion : This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. Trial registration : ClinicalTrials.gov Identifier NCT01589367Peer Reviewe