Expression of keratin 13, 14 and 19 in oral squamous cell carcinomas from Sudanese snuff dippers: lack of association with human papillomavirus infection

In stratified squamous epithelia, altered expression of keratins (Ks) is one possible marker of malignant potential. In the epithelium of the uterine cervix, presence of human papillomaviruses (HPVs) is increasingly regarded as a marker of risk for cervical cancer. However, a similar role in oral cancer and precancer remains controversial. To address these questions, formalin-fixed, paraffin-embedded oral carcinomas from Sudanese snuff dippers (n=14) and oral carcinomas from Sudanese (n=14), Swedish (n=19) and Norwegian (n=41) non-snuff dippers were examined by immunohistochemistry for expression of K types 13, 14 and 19 using monoclonal antibodies. HPV infection was searched for in all the carcinomas by in situ hybridization (ISH) using the cocktail HPV OmniProbe and the ViraType probe. Carcinomas from Sudanese (snuff dippers/non-snuff dippers) were also examined for HPV infection by polymerase chain reaction (PCR) using the general HPV primers GP5+/GP6+. For the oral carcinomas from snuff dippers, moderate to intense expression of K13 (71%; 10/14), K14 (86%; 12/14) and K19 (93%; 13/14) was found. For the oral carcinomas from non-snuff dippers, weak to moderate expression of K13 (64%; 47/74), K14 (43%; 32/74) and K19 (45%; 33/74) was found. HPV DNA was not detected in any of the carcinomas from three countries when examined by ISH. The Sudanese (from snuff dippers/non-snuff dippers) oral carcinomas were also negative for HPV DNA with the PCR. The present study shows that (i) there is a high level of expression of K13, K14 and K19 in oral carcinomas from snuff dippers compared to those from non-snuff dippers, (ii) this high level of expression may arise from dysregulation of keratinocyte proliferation and maturation caused by damaging effects of snuff, (iii) the HPV genome is not found in Sudanese (snuff dippers/non-snuff dippers), Swedish or Norwegian oral carcinomas, and (iv) this may suggest that these viruses do not play a prominent role in the aetiology of oral carcinomas from these countries.     

Rhinitis

Rhinitis is a problem causing significant morbidity. The etiology of rhinitis is varied. The pathophysiology of rhinitis is just beginning to be elucidated. Allergic rhinitis is primarily understood as an inflammatory disease with a neurogenic component. Disease states such as responses to cold dry air are primarily considered to be neurogenic in origin, but inflammatory cells and mediators play a significant role in the development of symptoms in these patients. Our understanding of these complex interactions is reflected in the pharmacologic interventions currently available. Most rhinitis therapy addresses the symptoms of rhinitis not the underlying disease state. Future research in the field of rhinitis should increase our knowledge of the pathophysiology and therefore assist in new drug development.     

Symmetry of normal motor and sensory nerve conduction measurements

Nerve conduction measurements in normal subjects are assumed to be symmetric, but the normal limits of symmetry have not been determined. Full data on the limits of symmetry for commonly studied nerves are important in the clinical interpretation of nerve conduction data. We selected normal electrodiagnostic studies from archived electromyographic laboratory reports that included bilateral measurements of motor and sensory nerves. Symmetry of nerve conduction measures was confirmed, and only the median and ulnar sensory nerves had significant deviations from symmetry, supporting subclinical nerve damage in the most common dominant hand. The limits of symmetry were determined by calculating the 95th percentile for the differences between sides. For motor and sensory nerves, the range of 95th percentile limits was narrower for measures in upper extremity nerves compared to lower extremity nerves. Several reasons are offered for the wider limits of symmetry in lower extremity nerves.     

A randomized trial of amitriptyline and mexiletine for painful neuropathy in HIV infection. AIDS Clinical Trial Group 242 Protocol Team

BACKGROUND: Painful sensory neuropathy is a common complication of HIV infection. Based on prior uncontrolled observations, we hypothesized that amitriptyline or mexiletine would improve the pain symptoms. METHOD: A randomized, double-blind, 10-week trial of 145 patients assigned equally to amitriptyline, mexiletine, or matching placebo. The primary outcome measure was the change in pain intensity between baseline and the final visit. RESULTS: The improvement in amitriptyline group (0.31+/-0.31 units [mean+/-SD]) and mexiletine group (0.23+/-0.41) was not significantly different from placebo (0.20+/-0.30). Both interventions were generally well tolerated. CONCLUSIONS: Neither amitriptyline nor mexiletine provide significant pain relief in patients with HIV-associated painful sensory neuropathy.     

MAdCAM-1 dependent colonization of developing lymph nodes involves a unique subset of CD4+CD3- hematolymphoid cells

During fetal lymph node organogenesis in mice, lymph node postcapillary high endothelial venules briefly express the Peyer's patch addressin MAdCAM-1. This allows initial seeding by two unusual lymphocyte populations selectively expressing the Peyer's patch homing receptor integrin alpha4beta 7: CD4+CD3- oligolineage progenitors and TCR gammadelta+ T cells. It was found that the CD4+CD3- cells are lineage-restricted progenitors that express surface lymphotoxin-beta (LTbeta) and the chemokine receptor BLR1. They can differentiate into natural killer cells, dendritic antigen-presenting cells, and follicular cells of unknown outcome, but these cells do not become T or B lymphocytes. In addition to LN, CD4+CD3- cells can also be found in fetal spleen starting at 13.5 dpc, while absent from fetal liver. In view of the necessity of lymphotoxin in lymphoid organ development, it is thought that the novel subset of CD4+CD3- LTbeta+ fetal cells is instrumental in the development of lymphoid tissue architecture.     

Preoperative staging of rectal carcinoma by magnetic resonance imaging with a pelvic phased-array coil

BACKGROUND: The use of surface coils for magnetic resonance imaging (MRI) allows enhanced image definition and so potentially more accurate staging of colorectal cancer. Endorectal coil imaging is invasive, operator dependent and impossible in a high proportion of patients due to rectal stricture. The phased-array pelvic coil, however, is non-invasive and applicable to all rectal tumours. METHODS: A pelvic phased-array coil was used for preoperative MRI staging of 38 primary rectal carcinomas. Results were expressed according to the Dukes and tumour nodes metastasis (TNM) classifications. After resection of the tumour, the stage predicted on MRI was compared with the pathological classification. RESULTS: The overall accuracy of preoperative staging with the pelvic phased-array coil was 55 per cent for both Dukes class and T stage. Assessment of nodal involvement gave an overall accuracy for MRI of 76 per cent with a sensitivity of 57 per cent and specificity of 88 per cent. CONCLUSION: Use of a pelvic phased-array coil did not improve the staging accuracy of MRI to a clinically useful level.     

Angiotensin II-induced tyrosine phosphorylation in mesangial and vascular smooth muscle cells

It has previously been suggested that paradigms investigating schema theory should include tests of the effects of variability of practice on tasks experienced during the acquisition of learning. The present aim was to test this effect using a sports-related task. Two groups of children (n = 13 each) aged between 3 and 5 yr. old were pretested on an aiming task. They then received ten practice trials per day for ten days. One group (designated the specific group) practised only at the specified target distance, while another group (designated the specific plus variable group) practised at the target distance and at distances around the target. At the end of the practice period both groups were again tested. The data were analysed for distance and lateral errors, using two-way (group x time) analyses of covariance with one repeated measure on the latter factor. The interaction of groups x time was significant for the distance errors, indicating that at the end of the practice period the specific plus variable group had improved more than the specific group. This finding extends previous work on a similar variability paradigm to a sports-related setting.     

Endothelin-A receptors mediate vascular smooth-muscle response to moderate acidosis in the canine tibial nutrient artery

Perfusate pH may influence the tone of vascular smooth muscle by affecting the release of endothelium-derived vasoactive factors or by directly modulating function of the smooth muscle. This study was designed to investigate the role of endothelium-derived factors on acidosis-induced responses of isolated canine tibial nutrient artery suspended in an organ chamber for the measurement of isometric contractile force. To investigate the specific role of the endothelium in half the rings, the endothelium was removed mechanically. Concentration-response curves to KCl were obtained in the absence or presence of inhibition of two important endothelium-derived relaxing factors, nitric oxide and prostacyclin, and an inhibitor of receptors for the endothelium-derived contracting factor, endothelin-1. Acidification of the perfusate from pH 7.45 to 7.0 significantly attenuated the contractions to KCl in arterial rings with endothelium (the mean of the effective concentration causing 50% of the maximal response for KCl at pH 7.45 and 7.0 was 12.31 +/- 0.40 nM and 14.60 +/- 0.55 nM, respectively). This difference was abolished by mechanical removal of the endothelium. In rings with endothelium, inhibition of nitric oxide or prostacyclin did not abolish the attenuation of KCl-induced contractions occurring with acidosis (the mean of the effective concentration causing 50% of the maximal response for KCl at pH 7.45 and 7.0 was 11.18 +/- 0.60 nM and 13.60 +/- 0.60 nM, respectively). Inhibition of endothelin-A receptors did not alter contractions to KCl at pH 7.45. However, the acidosis-induced attenuation of contractions with KCl was abolished by the endothelin-A-receptor antagonist BQ-123 (the mean of the effective concentration causing 50% of the maximal response at pH 7.45 and 7.0 was 13.8 +/- 1.34 nM and 13.2 +/- 1.34 nM, respectively). These results suggest that acidosis-induced relaxation of canine tibial nutrient artery is endothelium dependent and that activation of endothelin-A receptors during acidosis is coupled to a release of an endothelium-derived relaxing factor.     

Structural characterization of the O-antigenic polysaccharide of Escherichia coli serotype 017 lipopolysaccharide

Transverse nuclear magnetic relaxation and self-diffusion of water were measured in hydrated collagen II. Self-diffusion measurements were conducted by pulsed field gradient NMR (PFG NMR) and weighting of the different species in the signal by variable T2 relaxation in the experiment. Two fractions of water protons were detected, one with a short T2 value but high diffusivity and one with a long T2 value and low, completely restricted diffusion. The distance of the diffusion barriers was determined to be 2.3 microns. Possible reasons for the restriction in the movement of the water molecules in comparison with structural models of collagen II are discussed.