COX2 expression in neuroblastoma increases tumorigenicity but does not affect cell death in response to the COX2 inhibitor celecoxib

COX2 is an inducible cyclooxygenase implicated in the metastasis and migration of tumour cells. In neuroblastoma, COX2 expression has been detected in both cell lines and tumours. The treatment of neuroblastoma cells in vitro with celecoxib, a COX2 inhibitor, induces apoptosis. The aim of this study was to investigate the role of COX2 in neuroblastoma tumour biology by creating a cell line in which COX2 could be conditionally expressed. Xenograft studies showed that the conditional expression of COX2 enhanced tumour growth and malignancy. Elevated COX2 expression enhanced the proliferation and migration of neuroblastoma cells in vitro. However, elevated COX2 expression or variation between cell lines did not affect sensitivity to the COX2 inhibitor celecoxib, indicating that celecoxib does not promote cell death through COX2 inhibition. These data show that increased COX2 expression alone can enhance the tumorigenic properties of neuroblastoma cells; however, high levels of COX2 may not be a valid biomarker of sensitivity to non-steroidal anti-inflammatory drugs such as celecoxib.     

Skeletal muscle mRNA levels for cathepsin B, but not components of the ubiquitin-proteasome pathway, are increased in patients with lung cancer referred for thoracotomy

Muscle wasting is a common and prominent feature of advanced cancer, including lung cancer. Evidence from animal experiments suggests that accelerated proteolysis via the ubiquitin--proteasome pathway is the primary cause of cancer-related cachexia. However, there are few data on the role of this pathway in determining muscle wasting in human cancer. The present study was designed to measure whether skeletal muscle gene expression of components of the ubiquitin-proteasome pathway and/or the lysosomal proteolytic pathway was increased in patients with early lung cancer. A total of 36 patients with lung cancer referred for curative resection and 10 control subjects had biopsies of latissimus dorsi muscle taken at operation. mRNA levels of four components of the ubiquitin-proteasome pathway, i.e. polyubiquitin, C2 alpha proteasome subunit, 14 kDa ubiquitin-carrier protein and ubiquitin-activating protein, and of two lysosomal proteolytic enzymes, i.e. cathepsin B and cathepsin D, were measured using quantitative Northern blotting. mRNA levels for cathepsin B, but not for components of the ubiquitin--proteasome pathway, were higher in patients with cancer compared with controls (P=0.01). Among lung cancer patients, cathepsin B mRNA levels correlated with fat-free mass index (r = -0.57, P=0.003) and tumour stage (r(s)=0.45, P=0.03), and were higher in smokers (P=0.04). Thus gene expression of the lysosomal protease cathepsin B is increased in the skeletal muscle of patients with early lung cancer, and the strong inverse relationship with fat-free mass suggests that cathepsin B may have a role in inducing muscle wasting in the early stages of lung cancer.     

School based screening for hypothyroidism in Down's syndrome by dried blood spot TSH measurement.

OBJECTIVE: To determine the feasibility of annual hypothyroid screening of children with Down's syndrome by measuring thyroid stimulating hormone (TSH) on dried blood spots at school, and to describe the outcome in positive children. DESIGN: Establishment of a register of school children with Down's syndrome, and procedures for obtaining permission from parents, annual capillary blood samples, TSH measurement, and clinical assessment of children with TSH values > 10 mU/litre. SUBJECTS: All school age children with Down's syndrome within Lanarkshire and Glasgow Health Boards during 1996-7 and 1997-8. RESULTS: 200 of 214 school children with Down's syndrome were screened. Four of the unscreened children were receiving thyroxine treatment, and only 5 remained unscreened by default. 15 of the 200 children had capillary TSH > 10 mU/litre, and all but 1 had evidence of Hashimoto's thyroiditis. Seven of the 15 children started thyroxine treatment immediately, 6 with a pronounced rise in venous TSH and subnormal free thyroxine (fT4), and one with mildly raised TSH and normal fT4 but symptoms suggesting hypothyroidism. Eight children with mildly raised venous TSH and normal fT4 were left untreated; 1 year after testing positive, fT4 remained > 9 pmol/litre in all cases, but 4 children were started on thyroxine because of a rise in TSH. TSH fell in 3 of the 4 remaining children and there was a marginal rise in 1; all remain untreated. The prevalence of thyroid disease in this population is >/= 8.9%. CONCLUSION: Dried blood spot TSH measurement is effective for detecting hypothyroidism in Down's syndrome and capillary sampling is easily performed at school. The existing programme could be extended to the whole of Scotland within a few years.     

Sensory re-weighting in human postural control during moving-scene perturbations

The aim of the current study was to further investigate a recently proposed “sensory re-weighting” hypothesis, by evoking anterior–posterior (AP) body sway using visual stimuli during sway-referencing of the support surface. Twelve healthy adults participated in this study. Subjects stood on the platform while looking at a visual scene that encompassed the full horizontal field of view. A sequence of scene movements was presented to the subjects consisting of multiple visual push/pull perturbations; in between the first two push/pull sequences, the scene either moved randomly or was stationary. The peak-squared velocity of AP center-of-pressure (COP) was computed within a 6 s window following each push and pull. The peak-squared velocity was lowest for the push/pull sequence immediately following the random moving scene. These results are consistent with the sensory re-weighting hypothesis, wherein the sensory integration process reduced the contribution of visual sensory input during the random moving scene interval. We also found evidence of habituation to moving scene perturbations with repeated exposure.     

Nuclear retinoid receptor expression in normal human endometrium throughout the menstrual cycle

Previous work has shown that retinoic acid receptors (RARs)and retinoid X receptors (RXRs) are expressed in human endometrialepithelial and stromal cells. These nuclear receptors mediatethe biological effects of retinoic acid, a vitamin A derivativewhich may have an important, though poorly characterized rolein the functional differentiation of secretory eprthelia. Theaim of this study was to find out whether the expression ofRAR and RXR mRNA in endometrial epithelial and stromal cellsvaries in relation to the menstrual cycle. The expression ofRARs and RXRs was investigated by Northern blotting and, forstromal cells, there were no differences in expression of RAR-     

Oxidative phenotype protects myofibers from pathological insults induced by chronic heart failure in mice

The fiber specificity of skeletal muscle abnormalities in chronic heart failure (CHF) has not been defined. We show here that transgenic mice (8 weeks old) with cardiac-specific overexpression of calsequestrin developed CHF (50.9% decrease in fractional shortening and 56.4% increase in lung weight, P<0.001), cachexia (37.8% decrease in body weight, P<0.001), and exercise intolerance (69.3% decrease in running distance to exhaustion, P<0.001) without a significant change in muscle fiber-type composition. Slow oxidative soleus muscle maintained muscle mass, whereas fast glycolytic tibialis anterior and plantaris muscles underwent atrophy (11.6 and 13.3%, respectively; P<0.05). In plantaris muscle, glycolytic type IId/x and IIb, but not oxidative type I and IIa, fibers displayed significant decreases in cross-sectional area (20.3%, P<0.05). Fast glycolytic white vastus lateralis muscle showed sarcomere degeneration and decreased cytochrome c oxidase IV (39.5%, P<0.01) and peroxisome proliferator-activated receptor gamma co-activator 1alpha protein expression (30.3%, P<0.01) along with a dramatic induction of the MAFbx/Atrogin-1 mRNA. These findings suggest that exercise intolerance can occur in CHF without fiber type switching in skeletal muscle and that oxidative phenotype renders myofibers resistant to pathological insults induced by CHF.     

The impact of low-dose versus high-dose antibiotic prophylaxis regimens on surgical site infection rates after cesarean delivery

Archives of Gynecology and Obstetrics - The objective of this study was to determine if high-dose antibiotic prophylaxis with cefazolin decreases the risk of surgical site infection (SSI) after a...     

Association between esophageal dysmotility and gastroesophaeal reflux on barium studies

OBJECTIVE: To determine whether there is an association between abnormal primary peristalsis in the esophagus and gastroesophageal reflux (GER) on barium studies. METHODS: A computerized search of radiologic reports revealed 151 patients with esophageal dysmotility (characterized by intermittently decreased or absent peristalsis in the esophagus on upper gastrointestinal tract examinations) who fulfilled our study's entry criteria. These 151 patients were stratified into two groups depending on whether this dysmotility was associated with nonperistaltic contractions (NPCs): 92 patients had no NPCs (Dysmotility and No NPCs Group) and 59 had NPCs (Dysmotility and NPCs Group). An age-matched control group of 92 patients with normal motility was also generated from the radiologic reports. The reports were also reviewed for the presence and degree of GER and other complications of GER. The frequency and degree of GER were tabulated for each group, and the data were analyzed using a Pearson chi square test to determine if significant differences were present in the frequency and degree of GER or other findings among the groups. RESULTS: The frequency of GER was significantly higher in patients with abnormal peristalsis and no NPCs than in controls (p = 0.02). When GER was stratified based on the degree of reflux, the frequency of moderate-to-marked GER was significantly higher in patients with abnormal peristalsis and no NPCs than in patients with abnormal peristalsis and NPCs (p = 0.01) or in controls (p = 0.0031). The frequency of reflux esophagitis also was significantly higher in patients with abnormal peristalsis and no NPCs than in controls (p = 0.04). CONCLUSION: Our findings suggest that patients with esophageal dysmotility characterized by intermittently decreased or absent peristalsis without NPCs have a significantly higher frequency and degree of GER than patients with normal motility. The presence of this specific form of esophageal dysmotility on barium studies therefore should suggest underlying reflux disease.     

A mechanism for sensory re-weighting in postural control

A key finding of human balance experiments has been that the integration of sensory information utilized for postural control appears to be dynamically regulated to adapt to changing environmental conditions and the available sensory information, a process referred to as “sensory re-weighting.” We propose a postural control model that includes automatic sensory re-weighting. This model is an adaptation of a previously reported model of sensory feedback that included manual sensory re-weighting. The new model achieves sensory re-weighting that is physiologically plausible and readily implemented. Model simulations are compared to previously reported experimental results to demonstrate the automated sensory re-weighting strategy of the modified model. On the whole, the postural sway time series generated by the model with automatic sensory re-weighting show good agreement with experimental data, and are capable of producing patterns similar to those observed experimentally.