Folic acid reduces nuclear translocation of beta-catenin in rectal mucosal crypts of patients with colorectal adenomas

We have demonstrated that folic acid inhibits cell proliferation and epidermal growth factor receptor (EGFR) activation in colon cancer cell lines. We examined the effect of one year supplemental folic acid (5 mg/day) on the rectal mucosal expression of beta-catenin and pGSK3beta, known to be affected by EGF-R, in patients with colorectal adenomas. Folic acid treatment significantly reduced nuclear expression of beta-catenin (P < 0.05) and cellular expression of pGSK3beta (P < 0.01) when compared to placebo. Folic acid may exert its chemopreventive effect, at least in part, through inhibition of nuclear translocation of beta-catenin.     

Use of RT-PCR and DNA microarrays to characterize RNA recovered by non-invasive tape harvesting of normal and inflamed skin

We describe a non-invasive approach for recovering RNA from the surface of skin via a simple tape stripping procedure that permits a direct quantitative and qualitative assessment of pathologic and physiologic biomarkers. Using semi-quantitative RT-PCR we show that tape-harvested RNA is comparable in quality and utility to RNA recovered by biopsy. It is likely that tape-harvested RNA is derived from epidermal cells residing close to the surface and includes adnexal structures and present data showing that tape and biopsy likely recover different cell populations. We report the successful amplification of tape-harvested RNA for hybridization to DNA microarrays. These experiments showed no significant gene expression level differences between replicate sites on a subject and minimal differences between a male and female subject. We also compared the array generated RNA profiles between normal and 24 h 1% SLS-occluded skin and observed that SLS treatment resulted in statistically significant changes in the expression levels of more than 1,700 genes. These data establish the utility of tape harvesting as a non-invasive method for capturing RNA from human skin and support the hypothesis that tape harvesting is an efficient method for sampling the epidermis and identifying select differentially regulated epidermal biomarkers.     

Aging,physical activity,and cognitive processing: an examination of P300

Physical activity appears to attenuate the decline of cognitive function typically observed in older men and women. The P300 component of the event-related potential (ERP) is particularly affected by aging and allows for basic neurobiological assessment of cognitive function. Three aspects of the P300 component (i.e. latency, amplitude, and area under the curve (AUC)), elicited by an oddball task, were derived to assess cognitive function in young and older participants (N=73) who were further classified as high- and low-active. The low-active elderly participants exhibited larger AUC values than those observed in all other groups which were undifferentiated. That is, the high-active elderly and the young participants exhibited smaller AUC values than the low-active older group. In conclusion, higher levels of physical activity in the elderly may be associated with a reduction in the neural resources allocated in response to simple cognitive challenge. This interpretation is consistent with the concept of psychomotor efficiency proposed by Hatfield and Hillman [The psychophysiology of sport: a mechanistic understanding of the psychology of superior performance. In: Singer RN, Hausenbias HA, Janelle CM, editors. Handbook of sport psychology. 2nd ed. New York: Wiley; 2001, p. 362-88].     

Behavioral and electrocortical evidence of an interaction between probability and task metrics in movement preparation

Recent neurophysiological evidence suggests that cognitive factors shape neural activity in cortical areas such as parietal (area 5), premotor, and primary motor cortex. The implication of these findings is that behavioral signatures of cognitive factors and movement-specific factors should likewise be interdependent. The present study provides evidence of this interdependence in both behavioral (reaction time) and electrophysiological (P300) measures. Subjects performed a two-choice pointing task, in which the angular distance between the two required movement directions (task metrics) and the probability of the two responses was varied. In a control condition, a single reaction was required in response to both stimuli to test for the influence of stimulus metrics. Results from the pointing task showed a clear interaction between the metrics and effects of probability. When the potential targets were widely separated (120 degrees), stimulus probability influences reaction time and P300 amplitude in the classic fashion (longer reaction times and larger P300 amplitudes to less probable responses). When pointing to targets that were narrowly separated (20 degrees), probability had no effect: both rare and frequent targets were "functionally frequent." The same interaction was not observed in the control condition, indicating that metrics were primarily influencing movement preparation rather than stimulus processing. The results are consistent with the theoretical framework of dynamic field theory and demonstrate that metrics are an important factor that must be taken into account when assessing the processes associated with movement preparation.     

Spinal epidural abscess: a diagnostic challenge

The objective of the study was to highlight the diagnostic challenge of this elusive rare disease. A retrospective study of non-tuberculous spinal epidural abscesses (SEA) was carried out in Southern General Hospital, Glasgow, University Hospital of Wales, Cardiff, and Morriston Hospital, Swansea, from 1990 to 2000. Thirty-nine patients, consisting of 20 females and 19 males, with an age range from 20 to 85 years (mean: 61.1) were identified. Thirty-eight had localized back/neck pain. Eighteen were apyrexial. Twenty-nine demonstrated neurological deficit. All patients had raised inflammatory markers and gadolinium-enhanced magnetic resonance imaging (MRI) was diagnostic in 34. The most commonly identified organism was Staphylococcus aureus. All underwent surgical decompression, of which 13 required stabilization. Three died, seven lacked sphincter control and nine had motor deficit at the end of 1 year. It was concluded that fever is not mandatory for the diagnosis of SEA. Patients with localized back/neck pain and raised inflammatory markers need urgent MRI.     

1-Methylguanosine in place of Y base at position 37 in phenylalanine tRNA is responsible for its shiftiness in retroviral ribosomal frameshifting

Many mammalian retroviruses express their protease and polymerase by ribosomal frameshifting. It was originally proposed that a specialized shifty tRNA promotes the frameshift event. We previously observed that phenylalanine tRNA(Phe) lacking the highly modified wybutoxosine (Y) base on the 3' side of its anticodon stimulated frameshifting, demonstrating that this tRNA is shifty. We now report the shifty tRNA(Phe) contains 1-methylguanosine (m(1)G) in place of Y and that the m(1)G form from rabbit reticulocytes stimulates frameshifting more efficiently than its m(1)G-containing counterpart from mouse neuroblastoma cells. The latter tRNA contains unmodified C and G nucleosides at positions 32 and 34, respectively, while the former tRNA contains the analogous 2'-O-methylated nucleosides at these positions. The data suggest that not only does the loss of a highly modified base from the 3' side of the anticodon render tRNA(Phe) shifty, but the modification status of the entire anticodon loop contributes to the degree of shiftiness. Possible biological consequences of these findings are discussed.     

Glioma after cerebral hydatid disease

Background

The authors present the case of a 31-year-old man with a malignant glioma. He had been treated for cerebral hydatid as a child, and 22 years later he developed a glioma at the site of his previous disease.

Discussion

Could chronic inflammatory change following intracranial hydatid disease have induced neoplastic transformation of glial cells?