The role of epidemiology in cancer prevention

1. ISA Brown and Shaver 288 pullets were changed from 8 h to 8, 10, 13 or 16 h photoperiods at 42, 63, 84, 105, 126 or 142 d of age. 2. Age at first egg (AFE) was curvilinearly affected by the size and timing of the change in photoperiod. AFE was advanced most by a photoperiod change from 8 to 13 h made at 63 or 84 d. ISA birds were generally more responsive than Shaver to the photoperiod changes. 3. Longer photoperiods significantly increased survivors' egg production, but decreased liveability to 504 d. so that eggs per hen housed were unaffected. Retarding AFE by 10 d reduced survivors' egg numbers by 7.0, but increased mean egg weight by 1.26 g. Egg output by Shaver birds was unaffected by AFE, but that of ISA was curvilinearly affected, with an apogee at an AFE of 135 d. In both breeds, egg weight and egg output were greater following an early or late, rather than a mid-term photostimulation. 4. Photoperiod significantly increased mean daily food intake during lay by 1.26 g/h. A 10 d retardation in AFE resulted in a reduction in food intake of 1 g/d. Efficiency of food conversion deteriorated according to the square of the photoperiod, and changed curvilinearly according to age at photostimulation. Food conversion efficiency improved by 0.05 g/g for each 10 d delay in AFE. 5. Shell quality was unaffected by AFE, but deteriorated with increasing photoperiod and was curvilinearly affected by age at photostimulation with the smallest shell weights associated with photostimulation at 63 d. The incidence of double-yolked (DY) egg production increased with photoperiod and decreased with delayed photostimulation. There was an exponential regression of DY eggs on AFE. 6. Body weight at first egg increased by 75 g/d delay in AFE, but body weight at 504 d of age was unaffected by AFE, photoperiod or age at photostimulation. Body weight gain during lay increased by 15 g/h increase in photoperiod, decreased by 6 g per 10 d delay in photostimulation and by 40 g per 10 d delay in AFE. Fat content at 504 d increased by about 10 g/kg and by 23 g/bird for each 10 d delay in AFE. 7. Mortality in lay increased by 0.8%/h increase in photoperiod, but was unaffected by either age at photostimulation or AFE.     

Circulating soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in patients with gastric cancer

The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 45 patients with gastric cancer before treatment and their correlation with clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology, survival and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with gastric cancer in comparison with the group of healthy subjects (P < 0.00001 and P < 0.0001 respectively). Increased serum concentrations of VCAM-1 were associated with locally advanced and metastatic disease whereas ICAM-1 was significantly elevated both in local and in advanced/metastatic disease. Soluble E-cadherin and E-selectin concentrations did not show any significant elevation in gastric cancer patients. Concentrations of soluble adhesion molecules showed significant correlation with each other (except E-selectin and VCAM-1) and with alkaline phosphatase. Soluble ICAM-1 and VCAM-1 were significantly associated with an elevated total white cell count. Patients with elevated VCAM-1 had significantly poorer survival in comparison with patients with normal serum levels (P = 0.0361).     

Minor and major lip reconstruction

Lip reconstruction has made significant advances over the past two decades with refinement of some old techniques and the introduction of new innovative methods. Small and medium defects can be repaired in a variety of ways with similar results. Local lip switch flaps are far superior to any distant tissue. Total lip loss is probably best handled with nasolabial flaps. Extensive resections including the lip, premaxilla, mandible, and skin of the chin and upper neck remain a challenge with all modern techniques, including myocutaneous flaps and free flaps, having little advantage over the standard visor forehead flap.     

Redox control of exofacial protein thiols/disulfides by protein disulfide isomerase

Protein disulfide isomerase (PDI) facilitates proper folding and disulfide bonding of nascent proteins in the endoplasmic reticulum and is secreted by cells and associates with the cell surface. We examined the consequence of over- or underexpression of PDI in HT1080 fibrosarcoma cells for the redox state of cell-surface protein thiols/disulfides. Overexpression of PDI resulted in 3.6-4. 2-fold enhanced secretion of PDI and 1.5-1.7-fold increase in surface-bound PDI. Antisense-mediated underexpression of PDI caused 38-53% decreased secretion and 10-33% decrease in surface-bound PDI. Using 5,5'-dithio-bis(2-nitrobenzoic acid) to measure surface protein thiols, a 41-50% increase in surface thiols was observed in PDI-overexpressing cells, whereas a 29-33% decrease was observed in underexpressing cells. Surface thiol content was strongly correlated with cellular (r = 0.998) and secreted (r = 0.969) PDI levels. The pattern of exofacial protein thiols was examined by labeling with the membrane-impermeable thiol reactive compound, 3-(N-maleimidylpropionyl)biocytin. Fourteen identifiable proteins on HT1080 cells were labeled with 3-(N-maleimidylpropionyl)biocytin. The intensity of labeling of 11 proteins was increased with overexpression of PDI, whereas the intensity of labeling of 3 of the 11 proteins was clearly decreased with underexpression of PDI. These findings indicated that secreted PDI was controlling the redox state of existing exofacial protein thiols or reactive disulfide bonds.     

The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells

To assess the efficiency of nasally administered cartilage-specific collagens as vaccination against development of arthritis and to ameliorate already established chronic arthritis, experimental models which develop chronic arthritis, pristane-induced arthritis (PIA), and homologous collagen-induced arthritis (CIA) in the rat were selected. Cartilage-specific collagens type IX (CIX) and type II (CII) were used for vaccination intranasally. A single dose of 250 microg CII instilled intranasally in rats with established PIA ameliorated the disease. For the prevention of disease, the same dose given before immunization was found to be most effective. Most importantly, the disease was more severe if this dose was given three times. For treatment of PIA, CIX was found to be more effective than CII, whereas for treatment of CIA only CII was effective. The amelioration of CIA was associated with a marked suppression of delayed type hypersensitivity and the flare reaction to CII and lower levels of IgG2b anti-CII antibodies in serum, i.e., with suppression of the TH1 rather than the TH2 response to CII. These findings, that cartilage proteins, if given intranasally, can both prevent and ameliorate established chronic arthritis in rats, are of significant importance for possible use in rheumatoid arthritis. The identification of two different cartilage-specific proteins (CII and CIX) effective against a disease induced with a well-defined nonimmunogenic adjuvant such as pristane will be of value for enhancing the effectiveness of the treatment.     

A computational model for tracking subsurface tissue deformation during stereotactic neurosurgery

Recent advances in the field of stereotactic neurosurgery have made it possible to coregister preoperative computed tomography (CT) and magnetic resonance (MR) images with instrument locations in the operating field. However, accounting for intraoperative movement of brain tissue remains a challenging problem. While intraoperative CT and MR scanners record concurrent tissue motion, there is motivation to develop methodologies which would be significantly lower in cost and more widely available. The approach we present is a computational model of brain tissue deformation that could be used in conjunction with a limited amount of concurrently obtained operative data to estimate subsurface tissue motion. Specifically, we report on the initial development of a finite element model of brain tissue adapted from consolidation theory. Validations of the computational mathematics in two and three dimensions are shown with errors of 1%-2% for the discretizations used. Experience with the computational strategy for estimating surgically induced brain tissue motion in vivo is also presented. While the predicted tissue displacements differ from measured values by about 15%, they suggest that exploiting a physics-based computational framework for updating preoperative imaging databases during the course of surgery has considerable merit. However, additional model and computational developments are needed before this approach can become a clinical reality.