AIM: To investigate whether the combined methods of unilateral thyroparathyroidectomy (TPX) and subdiaphragmatic vagotomy (VAX) can be adapted for rats and used as a reliable method to produce a rat model of long-term reduction of gastrointestinal (GI) motor function.

METHODS: Male Sprague-Dawley rats were randomly divided into 3 groups, normal, sham-operated and unilateral TPX plus VAX. The TPX plus VAX rats received VAX 7 d after application of TPX, and dietary intake and fecal output were then measured daily for 1 wk. After completion of the experiments, gastric emptying and small bowel transit were measured in vivo, and the contractile responses of colonic strips to excitatory and inhibitory neurotransmitters were estimated using isometric force transducers in vitro.

RESULTS: In comparison with normal and sham-operated rats, rats which received unilateral TPX plus VAX showed a significant decrease in body weight and in fecal pellet number and weight throughout the entire week. Application of TPX plus VAX to rats markedly delayed gastric emptying and small bowel transit. In TPX plus VAX rats, the longitudinal muscles of the proximal colon showed a significant reduction in contractile responses to acetylcholine (5 × 10-6 mol/L), and a dramatic attenuation of contractile responses was also observed in both the longitudinal and circular muscles of the distal colon. However, the spontaneous contractility of the colonic strips from TPX plus VAX rats was not significantly affected by treatment with N-nitro-L-arginine-methyl ester (0.1 mol/L).

CONCLUSION: The results indicate that unilateral TPX plus VAX reduced the motor function of the GI tract in rats, and the reduced gut motility is likely mediated, at least in part, by inhibition of the excitatory neurotransmitter system.

Background

To evaluate the impact of diabetes on outcomes in colorectal cancer patients and to examine whether this association varies by the location of tumor (colon vs. rectum).

Patients and methods

This study includes 4,131 stage I-III colorectal cancer patients, treated between 1995 and 2007 (12.5% diabetic, 53% colon, 47% rectal) in South Korea. Cox proportional hazards modeling was used to determine the prognostic influence of DM on survival endpoints.

Results

Colorectal cancer patients with DM had significantly worse disease-free survival (DFS) [hazard ratio (HR) 1.17, 95% confidence interval (CI): 1.00–1.37] compared with patients without DM. When considering colon and rectal cancer independently, DM was significantly associated with worse overall survival (OS) (HR: 1.46, 95% CI: 1.11–1.92), DFS (HR: 1.45, 95% CI: 1.15–1.84) and recurrence-free survival (RFS) (HR: 1.32, 95% CI: 0.98–1.76) in colon cancer patients. No association for OS, DFS or RFS was observed in rectal cancer patients. There was significant interaction of location of tumor (colon vs. rectal cancer) with DM on OS (P = 0.009) and DFS (P = 0.007).

Conclusions

This study suggests that DM negatively impacts survival outcomes of patients with colon cancer but not rectal cancer.

Mucinous cystadenocarcinoma (MCA) in the breast is a rare neoplasm. There have been 13 cases of primary breast MCA reported. The MCA presents as a large, partially cystic mass in postmenopausal woman with a good prognosis. The microscopic findings resemble those of ovarian, pancreatic, or appendiceal MCA. The aspiration findings showed mucin-containing cell clusters in the background of mucin and necrotic material. The cell clusters had intracytoplasmic mucin displacing atypical nuclei to the periphery. Histologically, the tumor revealed an abundant mucin pool with small floating clusters of mucin-containing tumor cells. There were also small cysts lined by a single layer of tall columnar mucinous cells, resembling those of the uterine endocervix. The cancer cells were positive for mucin (MUC) 5 and negative for MUC2 and MUC6. This mucin profile is different from ordinary mucinous carcinoma and may be a unique characteristic of breast MCA.

Background

Skin-sparing mastectomy (SSM) and latissimus dorsi (LD) flap immediate breast reconstruction (IBR) is a tailored surgical procedure. The surgical and patient-reported outcome (PRO) of SSM and LD IBR were assessed.

Methods

Retrospective data of 146 SSMs performed by a single surgeon was reviewed. Among patients included in the data, 65 patients underwent SSM and LD IBR without a prosthetic implant. A survey estimating the degree of patient satisfaction (poor, fair, good, and excellent) as regards the cosmetic outcomes of surgery was performed. The patients were divided into two groups according to their degree of satisfaction (excellent group versus non- excellent group), and analysis was done to identify factors affecting the highest patient satisfaction.

Results

The mean age of the patients was 48.4 years, and pathological results were: infiltrating ductal carcinoma (n = 48, 73.8%), ductal carcinoma in situ (n = 15, 23.1%), and others (n = 2, 3.1%). One patient received postmastectomy radiotherapy. After a mean follow-up of 34 months, no local recurrence occurred. There was no skin necrosis or LD flap loss. Donor site morbidities were seroma (n = 8, 12.3%), scarring (n = 8, 12.3%), and back pain (n = 6, 9.2%). Fifty patients (76.9%) were satisfied and 40% reported their degree of satisfaction as excellent. Breast symmetry (P <0.001), nipple cosmesis (P <0.001), visual difference of bilateral breasts (P = 0.021), and panel assessment score (P <0.001) were factors that affected the highest patient satisfaction.

Conclusions

Our SSM and LD IBR was safe, with no local recurrence and low morbidities, and produced a sufficiently high level of patient satisfaction. Achieving breast symmetry and nipple cosmesis would be the key to meeting the patient’s expectation.

Neurogenic pulmonary edema (NPE) is a well-known complication of acute central neurologic injury, particularly aneurysmal subarachnoid hemorrhage. Both increased intracranial pressure and severe over-activation of the sympathetic nervous system seem to be pathogenetic for the onset of NPE. Although intracranial endovascular therapy is minimally invasive, it may affect brain stem regions and result in sympathetic activation. We now report the case of a 70-year-old woman who suddenly developed pulmonary edema during coil embolization of a ruptured aneurysm. During the intervention, oxygen saturation declined suddenly and a chest radiograph revealed pulmonary edema. The delayed appearance of NPE in this patient implies a risk for sympathetically mediated NPE during endovascular therapy.

Background

The purpose of this study was to investigate the association between obesity, fitness levels and cardiovascular (CVD) risk factors, and to identify the correlation between of insulin-like growth factor (IGF)-1, IGF binding protein-3 (IGFBP-3), and carotid intima media thickness (IMT) in Korean adolescents.

Methods

A total of 225 high school males with a mean age of 16.96±0.23 years participated in this study, and their fatness and fitness levels, fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), blood lipids, IGF-1, IGFBP-3, and IMT were measured.

Results

The results showed that total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), fasting insulin, HOMA-IR, IGF-1, and IGFBP-3 levels were significantly higher in the most obese group than in the other two groups (tertiles). Muscular and cardiopulmonary fitness were negatively associated with weight, body mass index (BMI), fat mass, body fat, waist circumference (WC), fasting insulin, HOMA-IR, and IMT. IGF-1 and IGFBP-3 levels were correlated with WC, hip circumference (HC), fasting glucose, TG, HDL-C, fasting insulin, and HOMA-IR. IMT levels were significantly associated with weight, BMI, muscle mass, fat mass, percent body fat, WC, HC, systolic blood pressure, diastolic blood pressure and high-sensitivity C-reactive protein.

Conclusion

There was a significant association between increased obesity and decreased fitness and HOMA-IR, IGF, and IMT among adolescents.

Acute generalized exanthematous pustulosis (AGEP) is manifested by rapid development of many sterile, nonfollicular pustules on a background of edematous erythema. More than 90 percent of AGEP are induced by medication, mostly antibiotics. Drug patch test can be helpful in the diagnosis of AGEP. This paper reports the first case of celecoxib-induced AGEP confirmed by patch test in Korean literature.

Background

Abscisic acid (ABA) is a plant hormone that controls seed germination, protective responses to various abiotic stresses and seed maturation. The ABA-dependent processes entail changes in gene expression. Numerous genes are regulated by ABA, and promoter analyses of the genes revealed that cis-elements sharing the ACGTGGC consensus sequence are ubiquitous among ABA-regulated gene promoters. The importance of the core sequence, which is generally known as ABA response element (ABRE), has been demonstrated by various experiments, and its cognate transcription factors known as ABFs/AREBs have been identified. Although necessary, ABRE alone is not sufficient, and another cis-element known as "coupling element (CE)" is required for full range ABA-regulation of gene expression. Several CEs are known. However, despite their importance, the cognate transcription factors mediating ABA response via CEs have not been reported to date. Here, we report the isolation of transcription factors that bind one of the coupling elements, CE1.

Results

To isolate CE1 binding proteins, we carried out yeast one-hybrid screens. Reporter genes containing a trimer of the CE1 element were prepared and introduced into a yeast strain. The yeast was transformed with library DNA that represents RNA isolated from ABA-treated Arabidopsis seedlings. From the screen of 3.6 million yeast transformants, we isolated 78 positive clones. Analysis of the clones revealed that a group of AP2/ERF domain proteins binds the CE1 element. We investigated their expression patterns and analyzed their overexpression lines to investigate the in vivo functions of the CE element binding factors (CEBFs). Here, we show that one of the CEBFs, AtERF13, confers ABA hypersensitivity in Arabidopsis, whereas two other CEBFs enhance sugar sensitivity.

Conclusions

Our results indicate that a group of AP2/ERF superfamily proteins interacts with CE1. Several CEBFs are known to mediate defense or abiotic stress response, but the physiological functions of other CEBFs remain to be determined. Our in vivo functional analysis of several CEBFs suggests that they are likely to be involved in ABA and/or sugar response. Together with previous results reported by others, our current data raise an interesting possibility that the coupling element CE1 may function not only as an ABRE but also as an element mediating biotic and abiotic stress responses.

Hydroa vacciniforme (HV) is a rare and chronic pediatric disorder that is characterized by photosensitivity and recurrent vesicles that heal with vacciniforme scarring. The pathogenesis of HV is unknown; no chromosome abnormality has been identified. HV patients have no abnormal laboratory results, so the diagnosis of HV is based on identifying the associated histological findings in a biopsy specimen and using repetitive ultraviolet phototesting to reproduce the characteristic vesicles on a patient's skin. Herein, we present a case of HV in a 7-year-old female who was diagnosed with HV according to histopathology and ultraviolet phototesting.

Lysophosphatidic acid (LPA) stimulates growth and invasion of ovarian cancer cells and tumor angiogenesis. Cancer-derived LPA induces differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) to α-smooth muscle actin (α-SMA)-positive cancer-associated fibroblasts. Presently, we explored whether cancer-derived LPA regulates secretion of pro-angiogenic factors from hASCs. Conditioned medium (CM) from the OVCAR-3 and SKOV3 ovarian cancer cell lines stimulated secretion angiogenic factors such as stromal-derived factor-1α (SDF-1α) and VEGF from hASCs. Pretreatment with the LPA receptor inhibitor Ki16425 or short hairpin RNA lentiviral silencing of the LPA1 receptor abrogated the cancer CM-stimulated expression of α-SMA, SDF-1, and VEGF from hASCs. LPA induced expression of myocardin and myocardin-related transcription factor-A, transcription factors involved in smooth muscle differentiation, in hASCs. siRNA-mediated depletion of endogenous myocardin and MRTF-A abrogated the expression of α-SMA, but not SDF-1 and VEGF. LPA activated RhoA in hASCs and pretreatment with the Rho kinase inhibitor Y27632 completely abrogated the LPA-induced expression of α-SMA, SDF-1, and VEGF in hASCs. Moreover, LPA-induced α-SMA expression was abrogated by treatment with the ERK inhibitor U0126 or the phosphoinositide-3-kinase inhibitor LY294002, but not the PLC inhibitor U73122. LPA-induced VEGF secretion was inhibited by LY294002, whereas LPA-induced SDF-1 secretion was markedly attenuated by U0126, U73122, and LY294002. These results suggest that cancer-secreted LPA induces differentiation of hASCs to cancer-associated fibroblasts through multiple signaling pathways involving Rho kinase, ERK, PLC, and phosphoinositide-3-kinase.

The Notch signaling pathway appears to perform an important function in a wide variety of organisms and cell types. In our present study, we provide evidence that UV irradiation-induced Tip60 proteins reduced Notch1 activity to a marked degree. Accumulated UV irradiation-induced Tip60 suppresses Notch1 transcriptional activity via the dissociation of the Notch1-IC-CSL complex. The binding between endogenous Tip60 and Notch1-IC in UV radiation-exposed cells was verified in this study by coimmunoprecipitation. Interestingly, the physical interaction of Tip60 with Notch1-IC occurs to a more profound degree in the presence of CSL but does not exist in a trimeric complex. Using Notch1-IC and Tip60 deletion mutants, we also determined that the N terminus, which harbors the RAM domain and seven ankyrin repeats of Notch1-IC, interacts with the zinc finger and acetyl coenzyme A domains of Tip60. Furthermore, here we report that Notch1-IC is a direct target of the acetyltransferase activity of Tip60. Collectively, our data suggest that Tip60 is an inhibitor of the Notch1 signaling pathway and that Tip60-dependent acetylation of Notch1-IC may be relevant to the mechanism by which Tip60 suppresses Notch1 signaling.

Eukaryotic DNA is organized into nucleosomes and higher order chromatin structure, which plays an important role in the regulation of many nuclear processes including DNA repair. Non-homologous end-joining, the major pathway for repairing DNA double-strand breaks (DSBs) in mammalian cells, is mediated by a set of proteins including DNA-dependent protein kinase (DNA-PK). DNA-PK is comprised of a large catalytic subunit, DNA-PKcs, and its regulatory subunit, Ku. Current models predict that Ku binds to the ends of broken DNA and DNA-PKcs is recruited to form the active kinase complex. Here we show that DNA-PK can be activated by nucleosomes through the ability of Ku to bind to the ends of nucleosomal DNA, and that the activated DNA-PK is capable of phosphorylating H2AX within the nucleosomes. Histone acetylation has little effect on the steps of Ku binding to nucleosomes and subsequent activation of DNA-PKcs. However, acetylation largely enhances the phosphorylation of H2AX by DNA-PK, and this acetylation effect is observed when H2AX exists in the context of nucleosomes but not in a free form. These results suggest that the phosphorylation of H2AX, known to be important for DSB repair, can be regulated by acetylation and may provide a mechanistic basis on which to understand the recent observations that histone acetylation critically functions in repairing DNA DSBs.