Up-regulation of cathepsin X in Helicobacter pylori gastritis and gastric cancer

Recently, we identified increased cathepsin X expression in H. pylori-infected gastric mucosa. Here, we describe further up-regulation in gastric cancer and report on the role of inflammatory cytokines required for cathepsin X up-regulation in H. pylori-infected gastric mucosa, as well as on consequences for cellular invasion. Biopsy specimens were taken from the antrum, corpus and cardia of H. pylori-infected and non-infected patients. Gastric cancer samples were obtained from patients undergoing gastric surgery. Cathepsin X was detected in gastric mucosa by quantitative real-time RT-PCR, western blotting and immunohistochemistry. Induction of cathepsin X expression in epithelial and inflammatory cells caused by H. pylori infection was tested in in vitro contact and non-contact co-cultures of AGS cells and monocytic cells. Patients with H. pylori gastritis showed significantly higher cathepsin X mRNA (2.5-fold) and protein (1.6-fold) expression than H. pylori-negative patients. Cathepsin X was also up-regulated in gastric cancer (3-12-fold) compared to non-neoplastic mucosa. Cathepsin X was predominantly expressed by macrophages in the mucosal stroma and in glands of the antral mucosa. In addition, tumour cells stained for cathepsin X in 26 (68%) patients with gastric carcinoma. In general, staining was significantly more common (20 vs. 6 patients) and more intense (3.55 vs. 0.83) in intestinal type gastric cancer than in the diffuse type. In vitro cell culture experiments revealed that intercellular signalling between pathogenicity island (PAI)-positive H. pylori-infected epithelial cells and macrophages via soluble factors in the culture medium seems to be responsible for increased expression of cathepsin X in monocytes. Using antisense oligonucleotides, cathepsin X up-regulation was directly associated with higher invasiveness in vitro. Although no correlation of cathepsin X expression and TNM stage was found, our study demonstrates that cathepsin X plays a role not only in the chronic inflammation of gastric mucosa but also in the tumourigenesis of gastric cancer.     

Selected components of physical fitness in rhythmic and artistic youth gymnast

Purpose

Rhythmic (RG) and artistic gymnastics (AG) are very popular female sports. These two disciplines share some common points but, at the same time, they display some relevant differences in terms of physical and technical characteristics. The aim of this study was as follows: (1) to clarify how gymnastic training background over the years could lead to the development and motor learning of the motor skills and (2) to highlight differences of conditional skills achieved by RG and AG athletes.

Methods

For these aims, 45 athletes were selected, belonging to three balanced groups: promotional (PG, n?=?15), RG (n?=?15), and AG (n?=?15). Participants were tested for joints mobility, balance, explosive strength, speed, and endurance tests.

Results

Statistical analysis showed a good test–retest reliability of the measurements (ICC?>?0.870) and some significant differences between PG, RG, and AG. RG showed higher values in joint mobility tests (coxo-femoral mobility, 166.7?±?6.3°; sit and reach, 20.5?±?1.9 cm; and scapulo-humeral mobility, 45.5?±?4.4 cm) with respect to AG, while AG showed higher values in endurance (1626.7?±?7.4 m), balance (4.33?±?1.35 n/60 s), and explosive strength (164.1?±?11.6 cm) compared to RG (p?<?0.05).

Conclusion

RG and AG seem to be effective in enhancing different and sport-specific physical fitness and conditioning. RG enables, indeed, to develop more joints mobility whereas AG improves more strength, balance, and endurance. However, given the small sample size employed, these results should be replicated by further studies utilizing larger samples.

     

IL-18-induced CD83+CCR7+ NK helper cells

In addition to their cytotoxic activities, natural killer (NK) cells can have immunoregulatory functions. We describe a distinct "helper" differentiation pathway of human CD56+CD3- NK cells into CD56+/CD83+/CCR7+/CD25+ cells that display high migratory responsiveness to lymph node (LN)-associated chemokines, high ability to produce interferon-gamma upon exposure to dendritic cell (DC)- or T helper (Th) cell-related signals, and pronounced abilities to promote interleukin (IL)-12p70 production in DCs and the development of Th1 responses. This helper pathway of NK cell differentiation, which is not associated with any enhancement of cytolytic activity, is induced by IL-18, but not other NK cell-activating factors. It is blocked by prostaglandin (PG)E2, a factor that induces a similar CD83+/CCR7+/CD25+ LN-homing phenotype in maturing DCs. The current data demonstrate independent regulation of the "helper" versus "effector" pathways of NK cell differentiation and novel mechanisms of immunoregulation by IL-18 and PGE2.     

Doppelbilder und Nasenatmungsbehinderung

Ohne Zusammenfassung

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Double images and handicaps to nasal breathing

     

Effect of exercise to exhaustion on myeloperoxidase and lysozyme release from blood neutrophils

Exercise sessions (swimming in rats and treadmill running in humans) resulted in stimulation of neutrophil degranulation in the experiments with animals and in the human study. Myeloperoxidase (MPO) (+67%) and lysozyme (+51%) quantities in the plasma of rats increased significantly immediately after exercise. The blood plasma lysozyme concentration was increased by 41% at the 6th min of treadmill exercise in athletes. The blood concentrations of neutrophil proteins normalized both in humans and animals at rest. The neutrophil protein concentrations in blood increased in parallel with the decrease of their level in leukocytes. The neutrophil capacity for an oxidative burst was not changed by the exercise, but decreased for 3–6 h in the post-exercise period. Such dynamics of the oxidative burst activity suggest a lack of association between this parameter and the degranulation process. The neutrophil proteins that appear in blood during degranulation can be involved in enhancing the bactericidal potency of blood, the activation of granulopoiesis, neutrophil efflux from bone marrow, and the conditioning of blood endothelium for leukocyte extravasation. Electronic Publication     

Topotecan (Hycamtin) responsiveness in human renal carcinoma cell lines of the clear cell and papillary types

BACKGROUND: Since no effective therapeutic approach is yet known for metastatic renal cell carcinoma (RCC), we analyzed the effects of topotecan (Hycamtin), a novel topoisomerase I-inhibitor, in RCC cell lines of the clear cell and papillary/chromophilic types. MATERIALS AND METHODS: The anti-proliferative and apoptosis-inducing effects of topotecan were analyzed in 20 RCC cell lines by MTT-assay and light microscopic apoptosis counting. Moreover, Bcl-2 and Bax expression was investigated by Northern blot and immunocytochemistry while the p53 mutation status was analyzed by DNA sequencing. RESULTS: Exposure to clinically relevant concentrations of topotecan (i.e. < or = 1 microg/ml) resulted in a significant (p<0.05) dose-dependent reduction of cell number in 17 out of 20 RCC cell lines. The reduction of cell number was paralleled by an increase in apoptotic cell death. Papillary/chromophilic RCCs exhibited a significantly (p<0.05) more pronounced responsiveness to topotecan than clear cell RCCs. Moreover, the effects of topotecan proved to be superior to those of 5-fluorouracil (5-FU), an anticancer drug currently used in the therapy of RCCs. No correlation became evident between responsiveness to topotecan and the expression levels of Bcl-2 and Bax. Moreover, the response to topotecan could not be correlated with the p53 mutation status of our RCC cell lines. CONCLUSION: Clinically relevant concentrations of topotecan induced apoptosis in RCC cell lines more effectively than 5-FU. Further testing will show whether topotecan-induced apoptosis can be exploited for the treatment of RCCs in vivo as well.