Invasive Papillary Carcinoma of the Breast Presenting as Post-Traumatic Recurrent Hemorrhagic Cysts

We report the sonographic features of an intracystic papillary carcinoma of the breast presenting as recurrent hemorrhagic cysts following trauma. A 56-year-old woman presented with palpable breast masses after a traumatic event; sonography showed multiple, well-defined, hemorrhagic cysts. Hemorrhagic fluid was evacuated by fine needle aspiration with no residual lesions. Cytology was negative for malignancy. Five months later, the mass reappeared; sonography demonstrated multiple cysts with solid nodules. US-guided core biopsy and surgery revealed invasive papillary carcinoma. We suggest close follow-up of cystic masses, even with negative cytology, and performance of surgical excisional biopsy in cases of rapid refilling after aspiration

The Effects of Glyburide on Apoptosis and Endoplasmic Reticulum Stress in INS-1 Cells in a Glucolipotoxic Condition

Backgroundβ-cell death due to endoplasmic reticulum (ER) stress has been regarded as an important pathogenic component of type 2 diabetes. The possibility has been suggested that sulfonylurea, currently being used as one of the main oral hypoglycemic agents of type 2 diabetes, increases ER stress, which could lead to sulfonylurea failure. The authors of the present study examined ER stress of β-cells in a glucolipotoxic condition using glyburide (GB) in an environment mimicking type 2 diabetes.MethodsApoptosis was induced by adding various concentrations of GB (0.001 to 200 µM) to a glucolipotoxic condition using 33 mM glucose, and the effects of varied concentrations of palmitate were evaluated via annexin V staining. The markers of ER stress and pro-apoptotic markers were assessed by Western blotting and semi-quantitative reverse transcription-polymerase chain reaction. Additionally, the anti-apoptotic markers were evaluated.ResultsAddition of any concentration of GB in 150 µM palmitate and 33 mM glucose did not increase apoptosis. The expression of phosphorylated eukaryotic initiation factor (eIF-2α) was increased and cleaved caspase 3 was decreased by adding GB to a glucolipotoxic condition. However, other ER stress-associated markers such as Bip-1, X-box binding protein-1, ATF-4 and C/EBP-homologous protein transcription factor and anti-apoptotic markers phosphor-p85 phosphatidylinositol 3-kinase and phosphorylation of Akt did not change significantly.ConclusionGB did not show further deleterious effects on the degree of apoptosis or ER stress of INS-1 cells in a glucolipotoxic condition. Increased phosphorylation of eIF-2α may attenuate ER stress for adaptation to increased ER protein load

Expression of GA733-Fc Fusion Protein as a Vaccine Candidate for Colorectal Cancer in Transgenic Plants

The tumor-associated antigen GA733 is a cell-surface glycoprotein highly expressed in colorectal carcinomas. In this study, 3 recombinant genes were constructed as follows: GA733 tagged to the ER retention sequence KDEL (GA733K), GA733 fused to the immunoglobulin Fc fragment (GA733-Fc), and GA733-Fc fused to the ER retention sequence (GA733-FcK). Agrobacterium-mediated transformation was used to generate transgenic plants expressing recombinant genes. The presence of transgenes was confirmed by genomic PCR. Western blot, confocal immunofluorescence, and sandwich ELISA showed the expression of recombinant proteins. The stability, flexibility, and bioactivity of recombinant proteins were analyzed and demonstrated through N-glycosylation analysis, animal trials, and sera ELISA. Our results suggest that the KDEL retained proteins in ER with oligomannose glycan structure and enhanced protein accumulation level. The sera of mice immunized with GA733-FcK purified from plants contained immunoglobulins which were at least as efficient as the mammalian-derived GA733-Fc at recognizing human colorectal cancer cell lines. Thus, a plant system can be used to express the KDEL fusion protein with oligomannose glycosylation, and this protein induces an immune response which is comparable to non-KDEL-tagged, mammalian-derived proteins

Odontogenic ameloblast-associated protein (ODAM) in gingival crevicular fluid for site-specific diagnostic value of periodontitis: a pilot study

Background Odontogenic Ameloblast-Associated Protein (ODAM) in gingival crevicular fluid (GCF) can provide evidence of the detachment of junctional epithelium from the tooth surface by periodontitis. This study sought to investigate the ability of ODAM to reflect the severity of periodontitis at a site-specific level; thus whether there was a relationship between clinical diagnostic parameters and the value of ODAM in GCF was analyzed. Methods Eight periodontitis patients with various severities were enrolled, and the clinical parameters and samples of GCF were obtained from 44 to 60 sites of each subject. The ODAM concentration was quantified by enzyme-linked immunosorbent assay. Correlation analyses between clinical parameters and ODAM values and unadjusted and adjusted (linear) mixed model analyses were performed. The accuracy of ODAM to reflect sites having a probing depth (PD) ≥ 5 mm and a positive bleeding on probing (BOP) was evaluated by receiver-operating characteristic analysis. Results A total of 424 GCF samples were collected. The mean ODAM concentration from each patient varied from 0.2 to 1.52 ng/ml. Correlations between PD or clinical attachment level (CAL) and ODAM values were found (p <  0.0001). An adjusted linear mixed model showed that PD or CAL were associated with ODAM values (p <  0.05). The area under the curve of ODAM, which reflected sites with PD ≥ 5 mm and positive BOP, was 0.661 (p <  0.0001). Conclusion This result shows the possibility of GCF ODAM as a site-specific biomarker for periodontal tissue destruction.This research was supported by a grant from the Korean Health Technology R&D project, Ministry of Health & Welfare, Republic of Korea (HI16C0220). The funder had no role in the design of the study and collection, analysis, and interpretation of data or in the writing of the manuscript

Insulin Level, RBC Na+ Transport and Blood Pressure in Cushing's Syndrome

To test the hypothesis that hyperinsulinemia and / or abnormalities of RBC Na+ transport are concerned in the pathogenesis of hypertension in Cushing's syndrome, we 'investigated the relationship between insulin level, RBC Na + transport and blood pressure in patients with Cushing's syndrome which is frequently associated with hyperinsulinemia, abnormalities of RBC Na + transport and hypertension. Both systolic and diastolic pressure were significantly higher in Cushing's syndrome than in normal subjects. Fasting serum insulin level was higher and both serum glucose and insulin responses after a 75g glucose load were significantly increased in patients with Cushing's syndrome as compared with normal subjects. Both RBC Na+ concentration and passive Na + permeability were significantly lower but Vmax of Na +, K+-pump was significantly higher in patients with Cushing's syndrome than in normal subjects, while Vmaxs of Na+-K+ cotransport and Na+-Li + countertransport were similar in the two groups. In multiple stepwise regression analysis for patients with Cushing's syndrome, fasting serum insulin level was directly correlated with both systolic and diastolic pressures (r=O. 52, p=O. 01; r=O. 51, p=O. 02, respectively). On the other hand,RBC Na + transport parameters showed little correlation with either systolic or diastolic pressures. These results suggest that hyperinsulinemia may contribute to the hypertension in Cushing's syndrome, but that the abnormalities of RBC Na + transport seen in Cushing's syndrome are not causally related to hypertension

Direct Reprogramming of Rat Neural Precursor Cells and Fibroblasts into Pluripotent Stem Cells

Background: Given the usefulness of rats as an experimental system, an efficient method for generating rat induced pluripotent stem (iPS) cells would provide researchers with a powerful tool for studying human physiology and disease. Here, we report direct reprogramming of rat neural precursor (NP) cells and rat embryonic fibroblasts (REF) into iPS cells by retroviral transduction using either three (Oct3/4, Sox2, and Klf4), four (Oct3/4, Sox2, Klf4, and c-Myc), or five (Oct3/4, Sox2, Klf4, c-Myc, and Nanog) genes. Methodology and Principal Findings: iPS cells were generated from both NP and REF using only three (Oct3/4, Sox2, and Klf4) genes without c-Myc. Two factors were found to be critical for efficient derivation and maintenance of rat iPS cells: the use of rat instead of mouse feeders, and the use of small molecules specifically inhibiting mitogen-activated protein kinase and glycogen synthase kinase 3 pathways. In contrast, introduction of embryonic stem cell (ESC) extracts induced partial reprogramming, but failed to generate iPS cells. However, when combined with retroviral transduction, this method generated iPS cells with significantly higher efficiency. Morphology, gene expression, and epigenetic status confirmed that these rat iPS cells exhibited ESC-like properties, including the ability to differentiate into all three germ layers both in vitro and in teratomas. In particular, we found that these rat iPS cells could differentiate to midbrain-like dopamine neurons with a high efficiency. Conclusions/Significance: Given the usefulness of rats as an experimental system, our optimized method would be useful for generating rat iPS cells from diverse tissues and provide researchers with a powerful tool for studying human physiology and disease