Flamingo cadherin: a putative host receptor for Streptococcus pneumoniae

Streptococcus pneumoniae fructose bisphosphate aldolase (FBA) is a cell wall-localized lectin. We demonstrate that recombinant (r) FBA and anti-rFBA antibodies inhibit encapsulated and unencapsulated S. pneumoniae serotype 3 adherence to A549 type II lung carcinoma epithelial cells. A random combinatorial peptide library expressed by filamentous phage was screened with rFBA. Eleven of 30 rFBA-binding phages inhibited 90% of S. pneumoniae adhesion to A549 cells. The insert peptide sequence of 9 of these phages matched the Flamingo cadherin receptor (FCR) when aligned against the human genome. A peptide comprising a putative FBA-binding region of FCR (FCRP) inhibited 2 genetically and capsularly unrelated pairs of encapsulated and unencapsulated S. pneumoniae strains from binding to A549 cells. Moreover, FCRP inhibited S. pneumoniae nasopharyngeal and lung colonization and, possibly, pneumonia development in the mouse intranasal inoculation model system. These data indicate that FBA is an S. pneumoniae adhesin and that FCR is its host receptor.     

Rapid detection of the CYP2A6*12 hybrid allele by Pyrosequencing? technology

Background  

Identification of CYP2A6 alleles associated with reduced enzyme activity is important in the study of inter-individual differences in drug metabolism. CYP2A6*12 is a hybrid allele that results from unequal crossover between CYP2A6 and CYP2A7 genes. The 5' regulatory region and exons 1–2 are derived from CYP2A7, and exons 3–9 are derived from CYP2A6. Conventional methods for detection of CYP2A6*12 consist of two-step PCR protocols that are laborious and unsuitable for high-throughput genotyping. We developed a rapid and accurate method to detect the CYP2A6*12 allele by Pyrosequencing technology.     

Hypoxia,tumour-associated macrophages,microvessel density,VEGF and matrix metalloproteinases in human gastric cancer: interaction and impact on survival

Introduction  

Hypoxia is a key feature of the microenvironment of cancer cells actively participating in tumour progression. Our study was aimed to evaluate the impact of hypoxia and hypoxia-associated factors on tumour progression and survival of patients with gastric cancer.     

Tumor-targeting nanodelivery enhances the anticancer activity of a novel quinazolinone analogue

GMC-5-193 (GMC) is a novel anticancer small-molecule quinazolinone analogue with properties that include antimicrotubule activity and inherent fluorescence. The aim of this study was to produce and optimize a systemically administered liposomal formulation for tumor-targeting delivery of GMC to enhance the anticancer effect of this compound and evaluate its bioefficacy. GMC was encapsulated within a cationic liposome, which was decorated on the surface with an anti-transferrin receptor single-chain antibody fragment (TfRscFv) as the tumor-targeting moiety to form a nanoscale complex (scL/GMC). Confocal imaging of fluorescent GMC uptake in a human melanoma cell line, MDA-MB-435, showed higher cellular uptake of GMC when delivered via the liposome complex compared with free GMC. Delivery of GMC by the tumor-targeting liposome nanoimmunocomplex also resulted in a 3- to 4-fold decrease in IC(50) values in human cancer cells [DU145 (prostate) and MDA-MB-435] compared with the effects of GMC administered as free GMC. In addition, the GMC nanoimmunocomplex increased the sensitivity of cancer cells to doxorubicin, docetaxel, or mitoxantrone by approximately 3- to 30-fold. In the MDA435/LCC6 athymic nude mice xenograft lung metastases model, GMC was specifically delivered to tumors by the nanoimmunocomplex. These data show that incorporation of small-molecule therapeutic GMC within the tumor-targeting liposome nanocomplex enhances its anticancer effect.     

Psychological problems in gastroenterology outpatients: A South Australian experience. Psychological co-morbidity in IBD,IBS and hepatitis C

Background

In independent studies, IBD, IBS and HCV have each been associated with a substantially increased risk of psychological problems such as depression and anxiety and impairment of quality of life compared to the general healthy population. However, the relative psychological burden for each of these diagnoses is unknown as it has never been compared contemporaneously at one institution. Current local data are therefore needed to enable an evidence-based allocation of limited clinical psychological resources.

Methods

Overall, 139 outpatients (64 IBD, 41 HCV, and 34 IBS) were enrolled in this cross-sectional study. The HADS, SCL90, SF-12 and appropriate disease-specific activity measures were administered. Differences between groups were assesed with ANOVA, the Chi-Square test and the independent samples t-test (two-tailed).

Results

Each of the three groups had significantly lower quality of life than the general population (p < 0.05). Overall, a total of 58 (42%) participants met HADS screening criteria for anxiety and 26 (19%) participants for depression. The HCV group had a significantly higher prevalence of depression than either of the other groups (HCV = 34%, IBS = 15% and IBD = 11%, p = 0.009). In the SCL90, the three disease groups differed on 7 out of 12 subscales. On each of these subscales, the HCV group were most severely affected and differed most from the general population.

Conclusion

Patients with these common chronic gastrointestinal diseases have significant impairment of quality of life. Anxiety is a greater problem than depression, although patients with HCV in particular, should be regularly monitored and treated for co-morbid depression. Evaluation of specific psychological interventions targeting anxiety is warranted.

     

Somatostatin in the elderly: diurnal plasma profile and secretory response to meal stimulation

Plasma somatostatin levels were determined during a 24-hour period and after a meal test in 7 and 5 elderly subjects (76-90 years), respectively. The data obtained were compared with those recorded in young adult subjects (22-30 years). Increased basal somatostatin values were found in elderly subjects (20.0 +/- 1.5 pg/ml) when compared to young adults (14.1 +/- 0.6 pg/ml; p less than 0.01). Also, the mean 24-hour somatostatin levels were higher in the elderly (21.3 +/- 0.8 pg/ml) than in young adults (16.7 +/- 0.5 pg/ml; p less than 0.01), and minor diurnal variations were found in the former group. The response to the meal test was less evident in the elderly than in the control group. The data obtained indicate an increased basal somatostatin production associated with a diminished variability throughout the 24-hour period and in relation to meals.     

Minimally invasive pharyngo-laryngo-esophagectomy: a salvage procedure for recurrent postcricoid esophageal cancer

Hypopharyngeal and cervical esophageal tumors represent 5-10% of all esophageal neoplasms and are challenging for both surgeons and oncologists, because the choice of the adequate therapeutic strategy is not clearly defined and therefore difficult. In fact, although surgical treatment represents the gold standard of therapy, chemo-radiotherapy, previously used as adjuvant treatment, has been more recently adopted with curative intent, leaving to surgery a salvage role only. When surgery is required it is advisable to reduce patients' trauma. The present study reports on a personal technique for minimally invasive pharyngo-laryngo-esophagectomy and reconstruction with the whole stomach. We use a laparoscopic approach for mobilization of the stomach, transhiatal esophageal dissection and to follow transhiatal gastric transposition to the neck combined to a cervicotomy to perform pharyngo-laryngectomy, proximal esophageal mobilization, and pharyngo-gastric anastomosis. We performed this technique on four patients with recurrent disease after initially curative primary chemo-radiotherapy. Mean operative time was 345 min (range: 300-384). There were no intraoperative complications. All patients were extubated immediately after the operation and were managed in postoperative care unit for a mean time of 10 days (range: 7-12). Enteral nutrition was begun on post-operative day (POD) 1. The nasogastric tube and drainages were removed on POD 11, and patients immediately started oral nutrition. One patient had a TIA (transient ischemic attack) on POD 2. All patients were discharged within 20 days (18-20). Initial experience with this minimally invasive technique in selected patients is encouraging because it seems to minimize postoperative complications and allows early rehabilitation.     

Effects of adult-onset calorie restriction on anxiety-like behavior in rats

Calorie restriction (CR) has consistently been shown to increase lifespan and ameliorate disease outcomes. Its effects on behavior are less clear, although anxiolytic-like effects have been observed. Rats were subjected to 1 of 4 dietary regimens: control, CR25%, CR50% and, an acute episode of CR and tested in 3 tests of anxiety: the open field test, the elevated plus maze, and the modified open field test. In the open field test, the CR25% and CR50% groups made more central zone entries than the control and Acute groups, which was primarily due to differences in the initial 5 min of the test. Moreover, both CR groups engaged in greater exploration of the central zone than the control group in the initial 5 min of the test. The Acute group also exhibited significantly longer latencies to leave the central zone at test onset than the control and CR50% group. In the elevated plus maze, the Acute group also displayed longer latencies to open arm entry as compared to the control and CR50% group and showed a lower ratio of open to total arm entries compared to all other groups. There were no effects of CR on any variable of the modified open field test. Possible neurochemical mechanisms underlying the anxiolytic-like effect of CR are discussed.