Robo1/Robo4: differential expression of angiogenic markers in colorectal cancer

The family of roundabout (Robo) proteins is related to the transmembrane receptors and plays a major role in the process of axonal guidance in neurogenesis. It has recently been shown that Robo proteins are also associated with tumor angiogenesis with Slit2 acting as the corresponding ligand. The aim of this study was to validate the differential expression by means of microarray analysis and real-time PCR and to analyze the in situ expression of Robo1 and Robo4 in colorectal cancer. Quantitative analyses of Robo1, Robo4 and Slit2 mRNA expression measured by large scale gene expression studies (Affymetrix U133A) showed a significant up-regulation of Robo1 in tumor vs. normal tissue, whereas Robo4 and Slit2 showed no significant deregulation. For subsequent real-time PCR experiments, paired colorectal tissue samples from cancerous and corresponding non-cancerous tissues were obtained from 50 colorectal cancer patients who underwent surgical resection. Robo1 mRNA overexpression in cancerous tissue compared with normal counterparts was observed in 80% of the patients with a 4-fold expression in 45% and a 12-fold expression in 15%. For Robo4, an up-regulation was detected in >70% (36/50). For Slit2, no differential expression was observed. The overexpression of Robo1 and Robo4 in tumor vs. normal tissue was verified using real-time PCR. The histological analysis revealed an expression of Robo1 mainly in tumor cells, whereas Robo4 is located primarily in endothelial cells of tumor vessels. Therefore, the Robo proteins provide potential target structures for the anti-tumorigenic and anti-angiogenic therapy of colorectal carcinoma.     

Results After Partial Left Ventriculectomy in a European Heart Failure Population

Abstract Background: Forty-nine consecutive patients undergoing partial left ventriculectomy (Batista) surgery between January 1995 and June 1998 were studied. Methods: Patient ages ranged from 12 to 85 years, and all patients were in New York Heart Association functional Class III or IV. Thirty-three patients had ischemic cardiomyopathy, and 16 had idiopathic myopathy. Inclusion criteria were left ventricular end diastolic volume index of < 150 mL/m², left ventricular ejection fraction of c 20%, or left ventricular end-diastolic diameter of > 70 mm. Sixteen patients were transplant candidates. Partial left ventriculectomy and mitral valve repair by means of a Cosgrove annuloplasty ring plus the Alfieri repair constituted only part of the complex cardiac reconstruction in 38 patients. Results: Five patients died early and five patients died late between 3 and 30 months postoperatively. The actuarial l-year survival rate was 81%. Twenty-seven patients with coronary artery disease underwent one to five bypass grafts when appropriate. In addition, three patients received aortic valve replacement, four received tricuspid valve repair, two received mitral valve replacement, and two underwent dynamic cardiomyoplasty. Left ventricular (LV) diameter could be reduced from a preoperative mean of 71 to 56 mm postoperatively. LV ejection fraction increased to 36% postoperatively. Ninety percent of patients are in New York Heart Association functional Class I or II. Conclusions: Patients with end-stage idiopathic or ischemic cardiomyopathies can be improved considerably with partial left ventriculectomy. Any cardiac comorbidity should be repaired simultaneously.     

Rapid detection of HBsAg and anti-HBs by enzyme-immunoassay

Enzyme-immunoassay (EIA) for HBsAg is a reliable method with third generation sensitivity. Using a mechanized system for washing and reading and computerized data processing, subnanogramme amounts of subtypes ad and ay could be detected in approx. 5.5 h.Using EIA-kit reagents and an HBsAg ‘standard’, anti-HBs could conveniently be detected. Sensitivity comparisons with dilution series of the WHO anti-HBs standard showed RIA to be 8–128 times more sensitive than EIA for anti-HBs. However, similar percentages of positives were found in a patient population, and discrepancies were found between RIA and EIA results which cannot be explained on the basis of sensitivity differences only. A careful examination of the specificity of EIA and RIA is indicated.     

Surfactant protein A, exposure to endotoxin, and asthma in garbage collectors and in wastewater workers

Endotoxin causes an inflammation at the bronchial and alveolar level. The inflammation-induced increase in permeability of the bronchoalveolar epithelial barrier is supposed to cause a leakage of pneumoproteins. Therefore, their concentrations are expected to increase in the bloodstream. This study aimed at examining the association between occupational exposure to endotoxin and a serum pneumoprotein, surfactant protein A, to look for nonoccupational factors capable of confounding this association, and examine the relation between surfactant protein A and spirometry. There were 369 control subjects, 325 wastewater workers, and 84 garbage collectors in the study. Exposure to endotoxin was assessed through personal sampling and the Limulus amebocytes lysate assay. Surfactant protein A was determined by an in house sandwich enzyme-linked immunosorbent assay (ELISA) in 697 subjects. Clinical and smoking history were ascertained and spirometry carried out according to American Thoracic Society criteria. Multiple linear regression was used for statistical analysis. Exposure was fairly high during some tasks in wastewater workers but did not influence surfactant protein A. Surfactant protein A was lower in asthmatics. Interindividual variability was large. No correlation with spirometry was found. Endotoxin has no effect on surfactant protein A at these endotoxin levels and serum surfactant protein A does not correlate with spirometry. The decreased surfactant protein A secretion in asthmatics requires further study.     

Interrelationship between TP53 gene deletion, protein expression and chromosome 17 aneusomy in gastric adenocarcinoma

Background  

This study evaluates the existence of numerical alterations of chromosome 17 and TP53 gene deletion in gastric adenocarcinoma. The p53 protein expression was also evaluated, as well as, possible associations with clinicopathological characteristics.     

Increased Ca2+ sensitivity of myofibrillar tension in ischaemic vs dilated cardiomyopathy

1. There is evidence that different aetiologies of heart failure, especially ischaemic vs dilated cardiomyopathy (ICM and DCM, respectively), may influence the prognosis of patients with this disease. Patients with ICM have a worse prognosis than those with DCM; the mechanisms underlying this difference have not yet been clarified. The aim of the present study was to investigate whether there are changes in myofibrillar function depending on the aetiology of human heart failure. 2. Ca²⁺‐dependent tension (DT) and actomyosin ATPase acitivity (MYO) in Triton X‐skinned fibre preparations of the left ventricular myocardium from patients with heart failure due to ICM (n = 5) and DCM (n = 5) were measured. Tension‐dependent ATP consumption was calculated by the ratio of DT and MYO (‘tension cost’). Non‐failing myocardium (NF) from donor hearts, which could not be transplanted because of technical reasons, was evaluated as a control. 3. Although DT was reduced, the myofibrillar Ca²⁺ sensitivity of DT and MYO, as well as tension cost, were increased in preparations from ICM and DCM myocardium compared with NF. The Ca²⁺ sensitivity of DT and MYO was significantly increased in ICM compared with DCM preparations, resulting in more economic cross‐bridge cycling in ICM than in DCM. 4. In conclusion, ICM is associated with an increased Ca²⁺ sensitivity of myofibrillar tension and ATPase activity accompanied by decreased tension cost compared with DCM. Thus, the worse prognosis associated with ICM does not seem to be due to differences in myofibrillar function.     

Identification of the amino-acetonitrile derivative monepantel (AAD 1566) as a new anthelmintic drug development candidate

Anthelmintic resistance has become a global phenomenon in gastro-intestinal nematodes of farm animals, including multi-drug resistance against the three major classes of anthelmintics. There is an urgent need for an anthelmintic with a new mode of action. The recently discovered amino-acetonitrile derivatives (AADs) offer a new class of synthetic chemicals with anthelmintic activity. The evaluation of AADs was pursued applying in vitro assays and efficacy and tolerability studies in rodents, sheep, and cattle. Amongst various suitable compounds, AAD 1566 eliminated many tested pathogenic nematode species, both at larval and adult stages, at a dose of 2.5 mg/kg bodyweight in sheep and 5.0 mg/kg bodyweight in cattle. The same doses were sufficient to cure animals infected with resistant or multi-drug-resistant nematode isolates. These findings, complemented by the good tolerability and low toxicity to mammals, suggest that AAD 1566, monepantel, would be a suitable anthelmintic drug development candidate.