Low cdc27 and high securin expression predict short survival for breast cancer patients

Cell cycle regulators cdc27 and securin participate in control of the mitotic checkpoint and survey the mitotic spindle to maintain chromosomal integrity. This is achieved by their functions in metaphase–anaphase transition, DNA damage repair, enhancement of mitotic arrest and apoptosis. We report on the roles of cdc27 and securin in aneuploidy and prognosis of breast cancer. The study comprises 429 breast cancer patients with up to 22 years of follow‐up. DNA content was determined by image cytometry, and immunopositivity for cdc27 and securin was based on tissue microarrays. An inverse association between cdc27 and securin expression was observed in both image cytometric and immunohistochemical analyses. Low cdc27 and high securin expression identified patients with significant difference in disease outcome. Cdc27 and securin immunoexpression identified patients at risk of early cancer death within five years from diagnosis. In multivariate analysis, the combination of cdc27 and securin immunohistochemistry was the strongest predictor of cancer death after lymph node status. We demonstrate, for the first time in human breast cancer, the prognostic value of cdc27 and securin immunohistochemistry. Cdc27 and securin appear promising biomarkers for applications in predicting disease progression, prognostication of individual patients and potential in anti‐mitotic drug development.     

LL-37 Opsonizes and Inhibits Biofilm Formation of Aggregatibacter actinomycetemcomitans at Subbactericidal Concentrations

Host defense peptides are immediate responders of the innate immunity that express antimicrobial, immunoregulatory, and wound-healing activities. Neutrophils are a major source for oral host defense peptides, and phagocytosis by neutrophils is a major mechanism for bacterial clearance in the gingival tissue. Dysfunction of or reduction in the numbers of neutrophils or deficiency in the LL-37 host defense peptide was each previously linked with proliferation of oral Aggregatibacter actinomycetemcomitans which resulted in an aggressive periodontal disease. Surprisingly, A. actinomycetemcomitans shows resistance to high concentrations of LL-37. In this study, we demonstrated that submicrocidal concentrations of LL-37 inhibit biofilm formation by A. actinomycetemcomitans and act as opsonins and agglutinins that greatly enhance its clearance by neutrophils and macrophages. Improved uptake of A. actinomycetemcomitans by neutrophils was mediated by their opsonization with LL-37. Enhanced phagocytosis and killing of A. actinomycetemcomitans by murine macrophage-like RAW 264.7 cells were dependent on their preagglutination by LL-37. Although A. actinomycetemcomitans is resistant to the bactericidal effect of LL-37, our results offer a rationale for the epidemiological association between LL-37 deficiency and the expansion of oral A. actinomycetemcomitans and indicate a possible therapeutic use of cationic peptides for host defense.     

Laparoscopic adrenalectomy in patients with subclinical Cushing syndrome

Background

Subclinical Cushing syndrome in patients with adrenal incidentalomas has been associated with an increased prevalence of the metabolic syndrome and cardiovascular risk. The management of these patients, be it conservative or surgical, is still debated, but there is accumulating evidence that surgery is best and that laparoscopic adrenalectomy, when possible, is the most preferred procedure. Here we present the short- and long-term results of laparoscopic adrenalectomy for subclinical Cushing syndrome and determine the effect of this procedure on components of the metabolic syndrome.

Methods

Twenty-nine patients, 8 men and 21 women with adrenal incidentalomas and subclinical Cushing syndrome who underwent laparoscopic adrenalectomy, were studied retrospectively. They had undergone postoperative follow-up for improvement or worsening of their arterial blood pressure, body weight, and fasting glucose level for a mean period of 77 months.

Results

Preoperatively, 17 patients (58.6 %) had arterial hypertension, 14 (48.3 %) had a body mass index exceeding 27 kg/m², and 12 (41.4 %) had diabetes mellitus. Postoperatively, a decrease in mean arterial pressure was found in 12 patients (70.6 %), a decrease in body mass index in 6 patients (42.9 %), and an improvement in glycemic control in 5 patients (41.7 %).

Conclusions

Laparoscopic adrenalectomy is beneficial in many patients with subclinical Cushing syndrome because it reduces arterial blood pressure, body weight, and fasting glucose levels. Prospective randomized studies are needed to compare laparoscopic adrenalectomy with a conservative approach and to confirm these results.     

Mammalian germ-line transgenesis by transposition

Transposons have been used in invertebrates for transgenesis and insertional mutagens in genetic screens. We tested a functional transposon called Sleeping Beauty in the one-cell mouse embryo. In this report, we describe experiments in which transposon vectors were injected into one-cell mouse embryos with mRNA expressing the SB10 transposase enzyme. Molecular evidence of transposition was obtained by cloning of insertion sites from multiple transgenic mice produced by SB10 mRNA/transposon coinjection. We also demonstrate germ-line transmission and expression from transposed elements. This technique has promise as a germ-line transgenesis method in other vertebrate species and for insertional mutagenesis in the mouse.     

Advanced intrahepatic cholangiocarcinoma in hepatitis C virus-related decompensated cirrhosis: case report and review of the literature

A 75-year-old man with no known previous liver disease was admitted to our institution because of right pleural effusion, backache, and pain in the upper right quadrant. Physical and laboratory work-up revealed decompensated liver cirrhosis. Spiral computed tomography (CT) showed a 6-cm tumour in the right liver lobe. Serum levels of aminotransferases, prothrombin time, total bilirubin, alphafetoprotein and carcinoembryonic antigen were within normal limits. However, the patient had elevated cholestatic enzymes, diffuse hypergammaglobulinaemia, a six-fold increase in carbohydrate antigen 19-9 (CA 19-9), cryoglobulinaemia, and reactivity against hepatitis C virus (anti-HCV). Although hepatocellular carcinoma is the most common cancer in a cirrhotic patient with chronic viral hepatitis, the investigation revealed the presence of intrahepatic cholangiocarcinoma (ICC). This is a less frequently occurring primary liver tumour, the aetiology and pathogenesis of which remain unclear in the majority of cases. The coexistence of HCV liver disease and ICC might be an incidental finding, but recently some reports have shown a relatively high incidence of this tumour in patients with HCV-related cirrhosis. The current aspects regarding ICC prevalence in HCV patients, the possible aetiopathogenetic links between this tumour and HCV, and the importance for ICC detection and characterization using the enhancement patterns with quadruple-phase spiral CT scan are also discussed.     

Myocardial performance index suggests optimal fluid loss during hemodialysis

Background

Patients on long‐term maintenance hemodialysis (HD) are at high risk of developing cardiovascular disease and suffering various cardiovascular complications during HD.

Hypothesis

The purpose of this study was to evaluate the influence of changing loading conditions on the myocardial performance index (MPI) in patients on long‐term HD and to specify an optimal level of fluid loss during HD that would maintain stable global cardiac function.

Methods

The study consisted of 52 patients with end‐stage renal failure (ESRF), mean age 56±11.7 y, range: 25–80 y, on regular HD. For each patient a complete echocardiographic‐Doppler examination was performed before and after HD. Systolic and diastolic parameters of left ventricular function were measured, and the myocardial performance index (MPI) was calculated.

Results

The MPI was significantly prolonged after HD (0.47±0.15 before HD versus 0.59±0.16 after HD, p < 0.001). Mean change in body weight during HD was 2.1±0.86 kg. The MPI did not change significantly in patients with intradialytic weight loss up to 1.75 kg.

Conclusions

The MPI value seems to be independent of acute preload changes only when fluid loss is less than 1.75 kg. A 1.75‐kg fluid loss during HD seems to be the optimal goal. In ESRF patients on HD, the MPI seems to be a good indicator of global left ventricular function and potentially a valuable aid in the effort to maintain optimal fluid balance. The authors have no funding, financial relationships, or conflicts of interest to disclose.     

Cardiac MRI: accuracy of simultaneous measurement of left and right ventricular parameters using three different sequences

BACKGROUND AND AIM: We evaluated a value of Qp/Qs (left-to-right shunt measurement) using volumetric cardiac magnetic resonance (CMR) cardiac output (CO) measurements. We defined intraobserver, interobserver variability and reproducibility of left and right ventricular parameters by CMR. Furthermore, we studied whether shortened acquisition time has an effect on the accuracy of left and right ventricular parameters both in healthy volunteers and in patients with cardiovascular disease. METHODS: Sixteen subjects were enrolled in this study. Group A (n = 8, five males) consisted of healthy volunteers with a mean age of 25.9 years (range 24-30). Group B (n = 8, four males) was heterogenic consisting of patients with left ventricular (LV) hypertrophy, hypertension or coronary artery disease with their mean age of 56.3 years (range 38-70). RESULTS: The measured Qp/Qs as calculated from the right and LV CO was 0.87 +/- 0.13. Overall variability [as presented with the lowest coefficient of variation (CV)%- the highest CV % of intraobserver, interobserver variability or reproducibility] of LV parameters were for ejection fraction (EF) 1.5-2.8%, stroke volume (SV) 1.3-3.2%, CO 1.4-3.2%, end-diastolic volume 0.5-3.0%, end-systolic volume 1.8-6.2% and LV mass 1.1-2.6%. Corresponding values for right ventricular parameters were for EF 1.1-4.2%, SV 1.9-8.2%, CO 1.9-7.6%, end-diastolic volume 2.1-7.6%, end-systolic volume 2.8-10.2% and right ventricle mass 2.9-8.3%. There was no statistically significant difference between the results of different sequences. CONCLUSIONS: The CMR allows accurate Qp/Qs observation but the absolute value is at slightly different level compared with reference methods. Both left and right ventricular parameters are highly reproducible and even small clinically relevant changes can be measured with CMR. The shortened acquisition does not affect significantly to the accuracy of CMR-derived parameters.     

rs2230201 polymorphism may dictate complement C3 levels and response to treatment in chronic hepatitis C patients

The basis of response of chronic hepatitis C (CHC) patients to treatment is still unclear, and there may be many other factors which influence treatment outcome other than the existing ones. The serum concentration of C3 closely reflects the total complement activity, and individuals affected by C3 deficiency suffer from recurrent pyogenic infections. This study aims to find out relationship between levels of C3 in serum and its functional SNPs with response to treatment. The study included 132 CHC patients of which 48 received Pegylated IFN+Ribavirin and 81 controls. C3 levels and its three known functional SNP's genotyped by ELISA and SSP PCR, respectively. C3 Level of the healthy group was significantly higher (88.5 ± 19 mg/dL) when compared to CHC group (56 ± 18 mg/dL; P < 0.001). Thirty‐three of 36 responders were rs2230201 CC genotype carriers, whereas 9 of 12 nonresponders were non‐CC genotype. The ‘C’ allele of rs2230201 was found to be associated with increased serum C3 levels when compared to other genotypes in healthy group, whereas CT genotype was associated with lowered serum C3 in CHC group. A serum C3 value of <53 mg/dL was predictive of SVR with sensitivity 63.89% and specificity 66.67%. The study supports the observation that rs2230201 ‘C’ allele is associated with increase of serum C3 levels when compared to ‘T’ allele which may confer advantage in attaining SVR when present in homozygous condition. The study suggests that patients with serum C3 value <53 mg/dL and non‐CC genotypes may not respond to treatment.