Analysis of Obesity-Related Factors and their Association with Aromatase Expression in Canine Malignant Mammary Tumours.

This study was designed to investigate the role of obesity in canine malignant mammary tumours (CMMTs), by assessing aromatase expression and the regulatory roles of immune mediators such as cyclo-oxygenase-2 (COX2), prostaglandin E2 (PGE2), nuclear factor kappa beta (NF-κB), hypoxia inducible factor-1α (HIF-1α) and adipokines (i.e. leptin) in lean, optimal body weight, overweight and obese animals. Clinicopathological data, including the breed, body weight, body condition score and age and neutering status, were collected, together with histopathological characteristics (i.e. histological types, grading and lymphatic invasion). To determine the expression of each factor, immunohistochemistry was conducted with 60 samples of malignant CMMTs. CMMTs from overweight and obese animals had significantly elevated levels of PGE2, and aromatase expression correlated significantly with PGE2, NF-κB and leptin expression. However, no significant difference was observed in terms of histopathological characteristics. The results suggest that PGE2, a known obesity-related immune mediator, could be upregulated in CMMTs from overweight and obese animals. In addition, PGE2, NF-κB and leptin influenced the expression of aromatase, as observed in women.

One-stage cosmetic finger reconstruction using a second toe island flap containing terminal branches of the toe artery.

INTRODUCTION: A finger reconstructed by toe transfer may have morphological defects. We report the results of second toe transfer for 1-stage finger reconstruction with an island flap based on terminal branches of the toe artery. HYPOTHESIS: The technique can improve the morphological outcomes of reconstructed fingers. MATERIALS AND METHOD: Between January 2008 and June 2011, toe-to-finger transfer was performed for 36 fingers in 31 patients. An island flap containing terminal branches of the toe artery was embedded in the neck of the second toe to eliminate the morphological defect caused by stenosis in that area. RESULTS: All reconstructed fingers and all flaps survived. No donor site complications occurred. The mean follow-up was 8 months (range, 5 to 25 months). The morphology of the reconstructed finger was close to that of a normal finger, and a natural transition could be observed in the finger pulp, the finger neck, and the junction between the toe and the finger. Sensory recovery of the finger pulp ranged from S1 to S3+. The mean pinch strength of the reconstructed fingers was 48% to 60% of that of the contralateral side. The mean DASH scores were 52.9, 48.9, and 46.0 for patients that had the index, third, and fourth fingers reconstructed, respectively, and the lowest mean aesthetic score was 70. DISCUSSION: The method provides good aesthetic and functional outcomes, and overcomes aesthetic difficulties associated with other methods of toe transfer for finger reconstruction.

Cytokeratin19 induced by HER2/ERK binds and stabilizes HER2 on cell membranes.

Cytokeratin19 (KRT19) is widely used as a biomarker for the detection of disseminated tumors. Using an LC-MS/MS proteomics approach, we found that KRT19 was upregulated in HER2-overexpressing cells and tissues. KRT19 expression was induced by HER2-downstream ERK at the transcriptional level. Another HER2-downstream kinase, Akt, was found to phosphorylate KRT19 on Ser35 and induce membrane translocation of KRT19 and remodeling of KRT19 from filamentous to granulous form. KRT19 phosphorylated by Akt could bind HER2 on the plasma membrane and stabilized HER2 via inhibition of proteasome-mediated degradation of HER2. Silencing of KRT19 by shRNA resulted in increased ubiquitination and destabilization of HER2. Moreover, treatment of KRT19 antibody resulted in downregulation of HER2 and reduced cell viability. These data provide a new rationale for targeting HER2-positive breast cancers.

Osteonecrosis of the hip in Korean patients with systemic lupus erythematosus: risk factors and clinical outcome.

OBJECTIVE: The objective of this paper is to identify the risk factors for development of symptomatic osteonecrosis (ON) and predictors of total hip replacement (THR) among systemic lupus erythematosus (SLE) patients in Korea. METHODS: The medical records of 1051 patients with SLE were reviewed, and 73 patients with symptomatic ON were identified. Among them, 64 patients were eligible for the analysis. Sixty-four age- and sex-matched SLE patients without apparent ON were included as disease controls. The risk factors for development of symptomatic ON were identified by logistic regression analyses. The predictors of THR were determined by Cox proportional hazards regression analyses. RESULTS: Among 64 patients with ON, 59 had ON of the hip and 36 underwent THR. Independent risk factors for development of symptomatic ON included Cushingoid body habitus (OR 21.792 (95% confidence interval (CI) 2.594-183.083)), use of cyclophosphamide (OR 2.779 (95% CI 1.106-6.981)) and azathioprine (OR 2.662 (95% CI 1.143-6.200)). In the Cox proportional hazards model, only advanced radiological stage of ON (Association for Research on Osseous Circulation (ARCO) stage) was a statistically significant predictor of THR. In subgroup analysis with stage I-III ON, multivariate Cox regression analysis showed neuropsychiatric SLE (NPSLE) (HR 6.295 (95% CI 2.178-18.192)) and cumulative prednisolone dose in the first six months after ON diagnosis > 0.9 g (HR 3.238 (95% CI 1.095-9.58)) to be independent predictors. CONCLUSIONS: Advanced ARCO stage at the onset of ON is an independent risk factor for THR in SLE patients with ON. In ARCO stage I-III ON, patients with NPSLE and those receiving > 0.9 g prednisolone during the first six months after the ON diagnosis are likely to require THR.

Meningitis in Korean patients with systemic lupus erythematosus: analysis of demographics, clinical features and outcomes; experience from affiliated hospitals of the Catholic University of Korea.

Meningitis is a rare complication of systemic lupus erythematosus (SLE), potentially leading to a fatal outcome. The demographic, clinical, and laboratory features, and the outcomes of meningitis were evaluated in Korean patients with SLE. In a retrospective medical record review of 1420 SLE patients, 20 patients who had developed septic or aseptic meningitis were identified. In 11 patients, the causative microorganisms were identified ('septic meningitis'), and Cryptococcus neoformans was the major pathogen. The other nine patients were diagnosed with aseptic meningitis. The patients with septic meningitis were older than those with aseptic meningitis (p = 0.025) and displayed mental changes more often (p = 0.005). Leukocyte counts in the cerebrospinal fluid (CSF) were higher (p = 0.044) and the levels of CSF glucose were lower in the septic meningitis group (p = 0.036). Plasma leukocyte counts and neutrophil counts were higher in patients with septic meningitis (p = 0.037 and p = 0.020, respectively). Meningitis was observed in 1.4% of Korean patients with SLE and, in 55% of the meningitis patients, microorganisms were isolated and Cryptococcus neoformans was most commonly identified. Altered mental status, plasma leukocytosis, neutrophilia, and CSF pleocytosis and hypoglycemia were more prominent in patients with septic meningitis.