Glial cell-induced endothelial morphogenesis is inhibited by interfering with extracellular signal-regulated kinase signaling.

PURPOSE: Tumor vasculature provides the infrastructure by which malignant tissue can be nourished; therefore, targeting angiogenesis may be an effective means of treating cancer. We showed previously that SNB19 glioblastoma cells modulate bovine retinal endothelial cells in cocultures to form capillary-like network structures, that matrix metalloproteinase-9 (MMP-9) expression is critical for endothelial morphogenesis, and that MMP-9 expression in glioblastoma cells is regulated by extracellular signal-regulated kinase-1 (ERK-1). In the present study, we investigated whether interfering with the activation of this mitogen-activated protein (MAP) kinase would repress MMP-9 synthesis and inhibit capillary formation. EXPERIMENTAL DESIGN: Cocultures of bovine retinal endothelial and SNB19 cells were analyzed for MMP-9 secretion, and phospho- and total ERK levels. These cocultures were treated with PD98059, a specific inhibitor of MAP/ERK kinase 1, or transfected with dominant-negative ERK-1 mutant containing expression vector. Alterations in capillary-like structure formation, and actin cytoskeleton and secretion of vascular endothelial growth factor (VEGF), MMP-9, and tissue inhibitor of metalloproteinase-1 were determined by immunofluorescence, gelatin zymography, and Western blotting. RESULTS: We found that inhibition of the ERK-1/2 pathway with PD98059 abrogated glial cell-mediated capillary formation by the endothelial cells and reduced the levels of MMP-9 in the coculture. Strikingly, the abrogation of MAP kinase signaling by a dominant-negative ERK-1 mutant inhibited glial-induced capillary network formation by reducing VEGF levels and MMP-9 activity and increasing the levels of tissue inhibitor of metalloproteinase-1. Inhibition of ERK activity also disrupted the formation of the actin cytoskeleton, a prerequisite for endothelial cell migration. CONCLUSION: The mechanism underlying activation of ERK is involved in reorganization of the actin cytoskeleton, and induction of VEGF and MMP-9, thereby stimulating endothelial cell morphogenesis. These studies clearly provide experimental evidence that ERK inhibition diminishes glial-induced endothelial-cell morphogenesis; therefore, interfering with ERK signaling may be a viable approach to target angiogenesis.     

Mouse mammary tumor virus-like gene sequences in breast tumors of Australian and Vietnamese women.

PURPOSE: There is considerable evidence that the presence of mouse mammary tumor virus (MMTV)-like gene sequences in human breast cancer is highly associated with human breast carcinoma. Previous studies have found MMTV-like gene sequences in 38% of breast cancer tissue from United States women. The prevalence of these sequences in Australian and Vietnamese women has never been reported. EXPERIMENTAL DESIGN: Using PCR and primers that amplify MMTV-like gene sequences, we tested cancerous and benign breast tissue from Caucasian-Australian, Vietnamese-Australian, and Vietnamese women. RESULTS: MMTV-like gene sequences were amplified in 19 of 45 (42.2%) archival breast cancer biopsy tissues from Caucasian-Australian women, but only 1 of 120 (0.8%) and 0 of 41 breast cancer biopsy tissues from Vietnamese and Vietnamese-Australian women, respectively. The same sequences were found in only 2 of 111 (1.8%) and 0 of 60 normal (benign) breast tissue samples from Australian and Vietnamese women, respectively. CONCLUSIONS: MMTV-like gene sequences are found in only some human populations and are rarely found in normal human breast tissue from all populations, suggesting they are not present in the normal human genome and have been acquired.     

In-person vs telephone-administered multiple-pass 24-hour recalls in women: validation with doubly labeled water

OBJECTIVE: To determine the accuracy of energy intakes estimated with the multiple-pass 24-hour recall method in women by conducting in-person and telephone interviews. Doubly labeled water measurements of total energy expenditure were used for validation. SUBJECTS: Thirty-five weight-stable women (mean age = 30 years, range = 19 to 46 years) participated. DESIGN: Total energy expenditure was measured over a 14-day period using the doubly labeled water method. During this time, 4 multiple-pass 24-hour recalls were obtained from the women (2 in-person, 2 by telephone) who were provided 2-dimensional food models to estimate portion sizes. The Food Intake Analysis System was used to analyze recall data. STATISTICAL ANALYSES: Paired t tests were conducted to examine differences between energy intake estimated from the telephone and in-person interviews. Agreement between the energy intake estimates from the telephone recalls and the in-person recalls was assessed using the technique of Bland and Altman. Paired t tests were used to compare energy intake estimated from the telephone and in-person recalls to total energy expenditure. RESULTS: No significant difference in mean daily energy intake was found between the telephone (2,253 +/- 688 kcal) and in-person (2,173 +/- 656 kcal) interviews (P = .36). However, the mean energy intake from each interview method was significantly lower than total energy expenditure (2,644 +/- 503 kcal) (P = .006 and .001, respectively). APPLICATIONS/CONCLUSIONS: Underreporting of energy intake was widespread in the sample. Although the multiple-pass 24-hour recall method did not generate a group measure of energy intake that was accurate or unbiased, the telephone-administered multiple-pass 24-hour recall was just as effective in estimating energy intake as the recall administered in-person. Dietetics professionals should be aware of the pervasive and serious problem of under-reporting of self-reported food intakes.     

Effects of a proton-pump inhibitor in cystic fibrosis

Most children with cystic fibrosis (CF) show persisting steatorrhoea even when treated with pancreatic enzyme. As a low duodenal pH could be responsible for this persisting fat loss, we evaluated the effects of a proton-pump inhibitor (lansoprazole) on both steatorrhoea and growth parameters in 15 CF patients, aged 3.1–22.6y. Acid steatocrit, anthropometry and dual-energy X-ray absorptiometry were used to evaluate steatorrhoea and the nutritional status before, during and 3 months after stopping lansoprazole treatment (15mg/d for 3 months). Mean ± SD acid steatocrit values decreased from 37.1 ± 8.8% to 28.5 ± 10.6% ( p = 0:02). Significant mean Z -score improvements were found for weight (+0:14; p = 0:02), height (+0:15; p = 0:03), subscapular (+0:61; p = 0:003), supra-iliac (+0:8; p = 0:002) and the sum of the four measured skinfolds (+0:61; p = 0:002). Z -scores deteriorated again after stopping lansoprazole. Fat mass and bone mineral content increased significantly on lansoprazole ( p = 0:008 and p = 0:005, respectively). We conclude that lansoprazole as adjuvant therapy significantly improves both steatorrhoea and the nutritional status in CF children who maintain steatorrhoea while on pancreatic enzymes.     

Aberrant crypt focus promotion and glucose intolerance: correlation in the rat across diets differing in fat, n-3 fatty acids and energy

McKeown-Eyssen (Cancer Epidemiol. Biomarkers Prevent., 3, 687-695, 1994) and Giovannucci (Cancer Causes Control, 6, 164-179, 1995), noting the striking similarity in lifestyle risk factors for colorectal cancer and insulin resistance, proposed that the hyperinsulinemia, glycemia and hypertriglyceridemia associated with insulin resistance promotes colon cancer. To compare the effect of diet on colon cancer promotion and insulin resistance in the F344 rat, we assessed the effect of fat, n-3 fatty acids and energy in pairwise comparisons on average size of aberrant crypt foci (ACF) and on glucose intolerance in the same animals in a single experiment. Diets high in fat and energy increased and diets with increased n-3 fatty acids and calorie restriction decreased both ACF growth and glucose intolerance compared with control diets. The measures of promotion of colon cancer and insulin resistance were strongly correlated (n = 98, r = 0.67, P < 0.001). In addition, both were highly correlated with daily energy intake (r = 0.62 and 0.66) and were also correlated with basal (post-prandial) insulin, glucose and triglycerides (r = 0.31-0.53, P < 0.01). We concluded that ACF growth and glucose intolerance are correlated for a wide range of diets and that increased circulating energy (glucose and triglycerides) may lead to both colon cancer promotion and insulin resistance.      

Creating a digital radiographic teaching file and database using a PC and common software

OBJECTIVE: We wanted to design an inexpensive, convenient database to store digital radiographic images of multiple formats. CONCLUSION: We designed a database that could be saved in a standard format using readily available software. Users of our database can save images in a Joint Photographic Experts Group (JPEG) format, allowing their easy incorporation into other programs.     

Predictors of operative outcome in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome

BACKGROUND: Plasma viral load has recently been associated with clinical outcome in patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). We hypothetized that, in addition to CD4 lymphocytes, plasma HIV-1 RNA counts are predictive of postoperative outcome. METHODS: HIV-infected and AIDS patients admitted to a major teaching hospital requiring invasive or surgical procedures were retrospectively analyzed for postoperative outcome. Preoperative and postoperative immune cell counts including plasma HIV-1 RNA counts were recorded. Chi-square analysis, Fisher's exact test, and multivariate regression were performed with statistical significance P 相似文献   

Interest of free flaps for cranial base reconstruction

We describe our experience in treating 7 patients who underwent skull base reconstruction with free flap (6 latissimus dorsi, 1 rectus abdominis) between October 1996 and November 1998. Four patients underwent temporal bone resection with auricular resection, 2 patients underwent anterior and middle cranial fossa resection, 1 patient underwent frontotemporal resection. There have been no failures of the free flaps and one cerebrospinal fluid leak. We advocate free flap reconstruction after temporal bone resection with auricular resection, and after anterior or middle cranial fossa resection when local flap options are not available or with complex dead space.     

Pretreatment of coir lignocellulose for preparation of a porous coir–polyurethane composite with high oil adsorption capacity

In this present work, different treatment methods of coir biomass were investigated to improve the oil sorption capacity. The treated coir material was then used to fabricate an efficient porous coir–polyurethane composite sorbent by incorporating coir into a polyurethane matrix. The new composite possessed an open cell structure with high porosity and high oil sorption efficiency. The suitable technical parameters of the coir treatment process were selected as: hot water treatment at 170 °C for 120 minutes. After treatment under this suitable condition, treated coconut fiber exhibited an oil adsorption capacity of 4.1 g g⁻¹, with an increase of 78.3% compared to that of the original coconut fiber. Furthermore, the application of the as-fabricated porous composite sorbent for oil treatment was examined under various conditions. It was observed that the oil uptake capacity of the new composite sorbent was high, up to 15.2 g g⁻¹ when 20% treated coir material with a particle size of 1 mm was added into the polyurethane matrix. Several advantages of the new porous composite sorbent obtained from coir biomass and polyurethane such as low cost, being eco-friendly, ready availability and high buoyancy make it an efficient sorbent material for oil spill treatment.

An efficient porous coir–polyurethane composite with high porosity and high oil sorption efficiency has been successfully prepared by incorporating coir into a polyurethane matrix.     

Cathepsins in neuronal plasticity

Proteases comprise a variety of enzymes defined by their ability to catalytically hydrolyze the peptide bonds of other proteins, resulting in protein lysis. Cathepsins, specifically, encompass a class of at least twenty proteases with potent endopeptidase activity. They are located subcellularly in lysosomes, organelles responsible for the cell's degradative and autophagic processes, and are vital for normal lysosomal function. Although cathepsins are involved in a multitude of cell signaling activities, this chapter will focus on the role of cathepsins(with a special emphasis on Cathepsin B) in neuronal plasticity. We will broadly define what is known about regulation of cathepsins in the central nervous system and compare this with their dysregulation after injury or disease. Importantly, we will delineate what is currently known about the role of cathepsins in axon regeneration and plasticity after spinal cord injury. It is well established that normal cathepsin activity is integral to the function of lysosomes. Without normal lysosomal function, autophagy and other homeostatic cellular processes become dysregulated resulting in axon dystrophy. Furthermore, controlled activation of cathepsins at specialized neuronal structures such as axonal growth cones and dendritic spines have been positively implicated in their plasticity. This chapter will end with a perspective on the consequences of cathepsin dysregulation versus controlled, localized regulation to clarify how cathepsins can contribute to both neuronal plasticity and neurodegeneration.