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Biomedical subjects

G Wu

Publications and source records attributed to G Wu.

At least 19 recordsLinked to original sources
PubMed2006

Histopathological characteristics of a novel knock-in mouse prostate cancer model.

Prostate cancer is relatively unique to man. There is no naturally occurring prostate cancer in the mouse. Pre-clinical studies involve the establishment of a genetically engineered mouse prostate cancer model with features close to those of the human situation. A new knock-in mouse adenocarcinoma prostate (KIMAP) model was established, which showed close-to-human kinetics of tumor development. In order to determine if the similar kinetics is associated with heterogeneous tumor architecture similar to the human situation, we utilized a new mouse histological grading system (Gleason analogous grading system) similar to the Gleason human grading system and flow cytometry DNA analysis to measure and compare the adenocarcinoma of the KIMAP model with human prostate cancer. Sixty KIMAP prostate cancer samples from 60 mice were measured and compared with human prostate cancer. Flow cytometry DNA analysis was performed on malignant prostate tissues obtained from KIMAP models. Mice with prostate cancer from KIMAP models showed a 53.3% compound histological score rate, which was close to the human clinical average (50%) and showed a significant correlation with age (P = 0.001). Flow cytometry analyses demonstrated that most KIMAP tumor tissues were diploid, analogous to the human situation. The similarities of the KIMAP mouse model with tumors of the human prostate suggest the use of this experimental model to complement studies of human prostate cancer.

Adenocarcinoma↗
PubMed2006

Hec1 sequentially recruits Zwint-1 and ZW10 to kinetochores for faithful chromosome segregation and spindle checkpoint control.

Faithful chromosome segregation is essential for maintaining the genomic integrity, which requires coordination among chromosomes, kinetochores, centrosomes and spindles during mitosis. Previously, we discovered a novel coiled-coil protein, highly expressed in cancer 1 (Hec1), which is indispensable for this process. However, the precise underlying mechanism remains unclear. Here, we show that Hec1 directly interacts with human ZW10 interacting protein (Zwint-1), a binding partner of Zeste White 10 (ZW10) that is required for chromosome motility and spindle checkpoint control. In mitotic cells, Hec1 transiently forms complexes with Zwint-1 and ZW10 in a temporal and spatial manner. Although the three proteins have variable cell cycle-dependent expression profiles, they can only be co-immunoprecipitated during M phase. Immunofluorescent study showed that Hec1 and Zwint-1 co-localize at kinetochores beginning at prophase and that ZW10 joins them later at prometaphase. Depletion of Hec1 impairs the recruitment of both Zwint-1 and ZW10 to kinetochores, while depletion of Zwint-1 abrogates the kinetochore localization of ZW10 but not Hec1. The results suggest that the localization of Hec1 at kinetochores is required for the sequential recruitment of Zwint-1 and ZW10. Disrupting this recruitment by inhibiting the expression of Hec1 or Zwint-1 causes chromosome missegregation, spindle checkpoint failure, and eventually cell death upon cytokinesis. Taken together, these results, at least in part, provide a molecular basis to explain how Hec1 plays a crucial role for spindle checkpoint control and faithful chromosome segregation.

Cell Cycle Proteins↗
PubMed2006

Vacuolar-type H+-ATPases at the plasma membrane regulate pH and cell migration in microvascular endothelial cells.

Microvascular endothelial cells involved in angiogenesis are exposed to an acidic environment that is not conducive for growth and survival. These cells must exhibit a dynamic intracellular (cytosolic) pH (pHcyt) regulatory mechanism to cope with acidosis, in addition to the ubiquitous Na+/H+ exchanger and HCO3--based H+-transporting systems. We hypothesize that the presence of plasmalemmal vacuolar-type proton ATPases (pmV-ATPases) allows microvascular endothelial cells to better cope with this acidic environment and that pmV-ATPases are required for cell migration. This study indicates that microvascular endothelial cells, which are more migratory than macrovascular endothelial cells, express pmV-ATPases. Spectral imaging microscopy indicates a more alkaline pHcyt at the leading than at the lagging edge of microvascular endothelial cells. Treatment of microvascular endothelial cells with V-ATPase inhibitors decreases the proton fluxes via pmV-ATPases and cell migration. These data suggest that pmV-ATPases are essential for pHcyt regulation and cell migration in microvascular endothelial cells.

Animals↗
PubMed2006

The relation of volume and outcome in trabeculectomy.

BACKGROUND/AIMS: Higher case volume has been associated with improved outcomes for a number of procedures. This study was designed to investigate whether this relationship existed for trabeculectomy. METHODS: The study was retrospective and conducted at an ophthalmic unit in the UK. All patients who had unenhanced trabeculectomy between 1996 and 2000 were identified. From their notes, the surgeon who performed the trabeculectomy was ascertained as were any unplanned interventions (eg conjunctival suturing, anterior chamber reformation, repeated attendances) within the first month of surgery. RESULTS: Two hundred and eleven trabeculectomies were performed over the study period. Twenty nine had unplanned interventions within the first postoperative month. Analysis of the data indicated that surgeons who performed less than eight operations per year had more complications than those who performed more than 10 per annum. This difference was only significant (chi(2)=4.0, P=0.045) when the data were aggregated. When separated per year, although not significant, the complication rate of the lower volume group was always higher than the group performing more than 10 per year. CONCLUSIONS: The results suggest that trabeculectomy can be added to the list of procedures in which larger case volume is associated with fewer early complications and potentially a better outcome. The findings, if replicated, tend to strengthen the argument for subspecialisation in glaucoma with its implications for training and revalidation.

Adult↗
PubMed2006

N-acetylglucosamine reduces inflammatory response during acute peritonitis in uremic rats.

BACKGROUND: Peritoneal dialysis (PD) induces intraperitoneal inflammation and that process may be uremia. The goal of this study is to evaluate the effect of uremia on the kinetics of peritonitis and furthermore test the anti-inflammatory potential of N-acetylglucosamine (NAG) in a uremic environment. METHODS: Experiments were performed on healthy Wistar rats and on animals with impaired renal function. Acute PD was performed in all animals with dialysis fluid containing either glucose (GLU) or NAG as osmotic solutes. Peritonitis was induced by addition of lipopolysaccharide from Escherichia coli (LPS) to the dialysis fluid. Transperitoneal transport of water and solutes as well as intraperitoneal and systemic inflammation were evaluated. RESULTS: Uremia reduces peritoneal permeability to total protein during peritonitis (-33% vs. control, p < 0.001) and increases net ultrafiltration (+2.5 +/- 2.2 vs. -2.7 +/- 3.2 ml in control, p < 0.001). In uremic rats with peritonitis, reduced dialysate levels of the following inflammatory mediators were detected as compared to healthy animals: MCP-1 (-15%, p < 0.01); IL-1beta (-53%, p < 0.001), and elastase (-28%, p < 0.02). In the serum of uremic rats, the increase in TNFalpha and MCP-1 concentrations was smaller than in control rats: -44% (p < 0.02) and -39% (p < 0.001), respectively. NAG used as an osmotic solute in rats with preserved renal function decreases intraperitoneal and systemic inflammation during acute peritonitis. Drained dialysate volume was increased in the NAG group by 32% (p < 0.001) and transperitoneal loss of protein was reduced by 21% (p < 0.002). When NAG was used as the osmotic solute instead of GLU, intraperitoneal inflammation in uremic animals was further reduced: TNFalpha (-40%, p < 0.05); IL-1beta (-49%, p < 0.005); MCP-1 (-21%, p < 0.005). The presence of NAG also reduced the increased blood level of IL-1beta (-47%,p < 0.02) and MCP-1 (-36%, p < 0.02). CONCLUSIONS: Intensity of acute peritonitis is reduced during uremia. NAG exerts a systemic and peritoneal anti-inflammatory action under conditions of uremia that confirms the potential use of this compound as an osmotic agent in the PD fluids that also decreases inflammation.

Acetylglucosamine↗
PubMed2006

Spontaneous intracerebral hemorrhage in humans: hematoma enlargement, clot lysis, and brain edema.

Early hematoma enlargement and delayed clot lysis contribute to brain injury after intracerebral hemorrhage (ICH). We investigated hematoma growth, clot lysis, and brain edema formation in patients with spontaneous ICH. A total of 17 spontaneous ICH patients who received regular medication were chosen for this study. All patients had their first CT scan within 5 hours of onset of symptoms (day 0). The patients then underwent second, third, and fourth CT scans at 1, 3, and 10 days later. Hematoma size and absolute and relative brain edema volumes were measured. Hematoma enlargement was defined as a > 33% increase in volume. Relative brain edema volume = absolute brain edema volume/hematoma size. Hematoma enlargement occurred in 4 of the 17 ICH patients (24%) within the first 24 hours. The hematoma sizes were reduced significantly at day 10 (p < 0.05) because of clot lysis. However, both absolute and relative brain edema increased gradually with time (p < 0.01). These results suggest that delayed brain edema following ICH may result from hematoma lysis. This study also shows that early hematoma enlargement occurs in Chinese patients with ICH. Reducing early hematoma growth and limiting clot lysis-induced brain toxicity could be potential therapies for ICH.

Brain Edema↗
PubMed2006

Nano-structural bioactive gradient coating fabricated by computer controlled plasma-spraying technology.

The poor mechanical property of hydroxyapatite was the major problem for load bearing and implant coating in clinical applications. To overcome this weakness, a bioactive gradient coating with a special design composition of hydroxyapatite (HA), ZrO2, Ti, bioglass was developed. This 120 microm coating with an upper layer of 30-50 microm porous HA produced by computer controlled plasma spraying which maintained energy level of the plasma which ensure proper melting of powder. The crystal size of the coating was 18.6-26.2 nm. Transformation of t-ZrO2 to m-ZrO2 reduced the thermal stress that weakened the coating and lowered down interfacial strength of the coating and metal substrate. Thermal stress of sprayed coating was 16.4 MPa which was much smaller than the sample without thermal treatment of 67.1 MPa. Interfacial strength between the coating and metal substrate was 53 MPa which is much higher than conventional Hydroxyapatite coating. Based on XRD analysis crystallinity of HA approached 98%. Therefore, high temperature treatment improved long term stability of the coating through improved crystallinity of hydroxyapatite and reduced other impure calcium phosphate phase.

Aluminum Oxide↗
PubMed2006

Comparison of Natuphos and Phyzyme as phytase sources for commercial layers fed corn-soy diet.

The objective of this experiment was to compare the effects of 2 sources of phytase on performance of commercial Leghorns fed corn-soy diets. Seven diets were fed to Hy-line W-36 hens (n = 840; 8 replicates of 15 hens per treatment) from 21 to 33 wk of age. The treatments consisted of a control diet containing 0.38% nonphytate P (NPP) and a 2 x 3 factorial arrangement of 2 dietary NPP concentrations (0.11 and 0.26%) with 2 phytase sources [Natuphos (BASF, Mt. Olive, NJ) and Phyzyme (Danisco Animal Nutrition, Carol Stream, IL)] and without phytase. Dietary NPP had significant effects on feed intake, NPP intake, total P intake, egg production, egg weight, egg mass, egg specific gravity, and excreta P. The addition of Phyzyme or Natuphos significantly increased egg production and egg mass of hens fed the P-deficient diet (0.11% NPP) to levels that were similar to hens fed the control diet containing 0.38% NPP. Feed intake of hens fed the diets supplemented with Phyzyme or Natuphos was significantly less than that of hens fed the control diet containing 0.38% NPP. Phyzyme or Natuphos supplementation in the diets containing 0.11% NPP had significantly reduced excreta P of the control diet (approximately 58 and 54%, respectively) with no adverse effect on egg production and egg mass. There were no significant differences in feed intake, NPP intake, total P intake, egg production, egg weight, egg mass, feed conversion, egg specific gravity, mortality, BW, and excreta P between the diets supplemented with Natuphos and the diets supplemented with Phyzyme. In conclusion, Phyzyme had the same positive effects on performance of commercial Leghorns fed corn-soy diets as Natuphos.

6-Phytase↗
PubMed2006

Application of Gleason analogous grading system and flow cytometry DNA analysis in a novel knock-in mouse prostate cancer model.

OBJECTIVE: A new knock-in mouse adenocarcinoma prostate model (KIMAP) was established, which showed a close to human kinetics of tumour development. This study used a new mouse histological grading system similar to the human Gleason grading system and flow cytometry DNA analysis to measure and compare the new KIMAP model with human CaP and transgenic mouse adenocarcinoma prostate (TGMAP) model. METHODS: According to heterogeneity of the clinical standard for prostate cancer diagnosis, a close to human mouse standard for histological grading and scoring system, Gleason analogous grading system, was established in this study. Sixty KIMAP and 48 TGMAP prostate cancer samples were measured and compared with human CaP. Flow cytometry DNA analysis was performed on malignant prostate tissues obtained from both TGMAP and KIMAP models. RESULTS: Mice with CaP from KIMAP (n = 60) and TGMAP (n = 48) models showed a different distribution of histological scores (p = 0.000). KIMAP mice showed higher percentage (53.3%) of compound histological score rate than TGMAP (25%), but closer to the human clinical average (50%), which showed significant correlation with age (p = 0.001), while TGMAP mice showed unbalanced and random score distribution in all age groups. Flow cytometry analyses showed that most tumour tissues in KIMAP were diploid, analogous to the human condition, while all the TGMAP mice showed aneuploid tumours. CONCLUSIONS: Results of this study further show that KIMAP, a new generation of murine prostate cancer model, could be used as a supplementary model in addition to the currently widely used transgenic models.

Adenocarcinoma↗
PubMed2006

Board-invited review: intrauterine growth retardation: implications for the animal sciences.

Intrauterine growth retardation (IUGR), defined as impaired growth and development of the mammalian embryo/fetus or its organs during pregnancy, is a major concern in domestic animal production. Fetal growth restriction reduces neonatal survival, has a permanent stunting effect on postnatal growth and the efficiency of feed/forage utilization in offspring, negatively affects whole body composition and meat quality, and impairs long-term health and athletic performance. Knowledge of the underlying mechanisms has important implications for the prevention of IUGR and is crucial for enhancing the efficiency of livestock production and animal health. Fetal growth within the uterus is a complex biological event influenced by genetic, epigenetic, and environmental factors, as well as maternal maturity. These factors impact on the size and functional capacity of the placenta, uteroplacental blood flows, transfer of nutrients and oxygen from mother to fetus, conceptus nutrient availability, the endocrine milieu, and metabolic pathways. Alterations in fetal nutrition and endocrine status may result in developmental adaptations that permanently change the structure, physiology, metabolism, and postnatal growth of the offspring. Impaired placental syntheses of nitric oxide (a major vasodilator and angiogenic factor) and polyamines (key regulators of DNA and protein synthesis) may provide a unified explanation for the etiology of IUGR in response to maternal undernutrition and overnutrition. There is growing evidence that maternal nutritional status can alter the epigenetic state (stable alterations of gene expression through DNA methylation and histone modifications) of the fetal genome. This may provide a molecular mechanism for the role of maternal nutrition on fetal programming and genomic imprinting. Innovative interdisciplinary research in the areas of nutrition, reproductive physiology, and vascular biology will play an important role in designing the next generation of nutrient-balanced gestation diets and developing new tools for livestock management that will enhance the efficiency of animal production and improve animal well being.

Animal Husbandry↗
PubMed2006

Severe vitamin D deficiency in chronic renal failure patients on peritoneal dialysis.

UNLABELLED: The aim of this study was to evaluate the prevalence of vitamin D deficiency in chronic renal failure (CRF) patients on peritoneal dialysis (PD) and to correlate the findings with various demographic and renal osteodystrophy markers. METHOD: This cross-sectional, multicenter study was carried out in 273 PD patients with a mean age of 61.7 +/- 10.9 years and mean duration of PD 3.3 +/- 2.2 years. It included 123 female and 150 male patients from 20 centers in Greece and Turkey, countries that are on the same latitude, namely, 36-42 degrees north. We measured 25(OH)D3 and 1.25(OH)2D3 levels and some other clinical and laboratory indices of bone mineral metabolism. RESULTS: Of these 273 patients 92% (251 patients) had vitamin D deficiency i.e. serum 25(OH)D3 levels less than 15 ng/ml, 119 (43.6%) had severe vitamin D deficiency i.e., serum 25(OH)D3 levels, less than 5 ng/ml, 132 (48.4%) had moderate vitamin D deficiency i.e., serum 25(OH)D3 levels, 5-15 ng/ml, 12 (4.4%) vitamin D insufficiency i.e., serum 25(OH)D3 levels 15 - 30 ng/ml and only 10 (3.6%) had adequate vitamin D stores. We found no correlation between 25(OH)D3 levels and PTH, serum albumin, bone alkaline phosphatase, P, and Ca x P. In multiple regression analyses, the independent predictors of 25(OH)D3 were age, presence of diabetes (DM-CRF), levels of serum calcium and serum 1.25(OH)2D3. CONCLUSION: We found a high prevalence (92%) of vitamin D deficiency in these 273 PD patients, nearly one half of whom had severe vitamin D deficiency. Vitamin D deficiency is more common in DM-CRF patients than in non-DM-CRF patients. Our findings suggest that these patients should be considered for vitamin D supplementation.

Adult↗
PubMed2005

Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover.

AIMS/HYPOTHESIS: Increased circulating methylarginines (MA) have been linked to the metabolic syndrome to explain endothelial dysfunction and cardiovascular disease risk. Proteins that contain MA are regulatory and release them during catabolism. We hypothesised that increased protein turnover in insulin-resistant states contributes to an increase in circulating MA. MATWERIALS AND METHODS: We performed hyperinsulinaemic, euglycaemic, and isoaminoacidaemic experiments on 49 lean, obese and elderly subjects, with measurements of the kinetics of glucose and protein metabolism. Plasma MA, i.e. asymmetrical dimethylarginine (ADMA), symmetrical dimethylarginine (SDMA), and N -monomethyl-L-arginine (NMMA), lipids and body composition were measured. RESULTS: Insulin resistance of glucose and protein metabolism occurred in obese and elderly subjects. ADMA concentrations were 29 to 120% higher in obese and 34% higher in elderly than in lean subjects. SDMA were 34 and 20% higher in obese than in lean and than in elderly subjects, respectively. NMMA were 32% higher in obese than in lean subjects. ADMA differed by sex, being higher in men, namely by 1.75x in obese men and by 1.27x in elderly men. Postabsorptive ADMA (r=0.71), SDMA (r=0.46), and NMMA (r=0.31) correlated (all p<0.05) with rates of protein flux. All three MA correlated negatively with clamp glucose infusion rates and uptake (p<0.001). ADMA and SDMA correlated negatively with net protein synthesis and clamp amino acid infusion rates (p<0.05). All MA also correlated with adiposity indices and fasting insulin and triglycerides (p<0.05). CONCLUSIONS/INTERPRETATION: Obesity, sex and ageing affect MA. Elevations of the three MA in obese, and of ADMA in elderly men, are related to increased protein turnover and to lesser insulin sensitivity of protein metabolism. These interrelationships might amplify insulin resistance and endothelial dysfunction.

Adult↗
PubMed2005

Effects of venom defibrase on brain edema after intracerebral hemorrhage in rats.

We evaluated the effects of defibrase DF-521 batroxobin on reducing brain edema formation and the expression of ICAM-1, complement C3d and C9 in the perihematomal area after intracerebral hemorrhage (ICH) in rats. A rat ICH model, involving infusion of autologous blood into the right basal ganglia, were used in this study. The animals were sacrificed at 24 and 72 hours after ICH to determine the water content of the brain tissue with wet/dry weight measurement. While the expression of ICAM-1 and complement C3d was detected using immuno-histochemistry, and C9 was detected semi-quantitatively with Western blot analysis in the perihematomal area. Perihematomal brain edema was reduced after intraperitoneally injection of DF-521 batroxobin 24 and 72 hours after intracerebral hemorrhage. Immunohistochemistry showed that there were less ICAM-I positive cells were found around the hematoma after intraperitoneally injection of DF-521 batroxobin 24 and 72 hours after ICH. Immuno-histochemistry also showed that C3d deposition reduced significantly, and the Western blot analysis also showed the content of C9 protein declined around the hematoma in DF-521 batroxobin treatment group at 72 hours after ICH. Defibrase DF-521 batroxobin down-regulate ICAM-1 and complement C3d and C9 expression in the perihematomal area, and attenuate brain edema formation in ICH rats.

Animals↗
PubMed2005

Effect of dietary energy on performance and egg composition of Bovans White and Dekalb White hens during phase I.

A 4 x 2 factorial experiment with 4 dietary energy levels (2,719, 2,798, 2,877, and 2,959 kcal of ME/ kg) and 2 strains (Bovans White and Dekalb White) was conducted to determine the effect of dietary energy on reproductive performance, egg composition, and profits of 2 strains of commercial Leghorns. This experiment lasted 16 wk. Bovans White hens (n = 768) and Dekalb White hens (n = 768) in phase I (21 wk of age) were randomly assigned into 8 treatments (16 replicates of 12 birds/treatment). Bovans White had significantly higher feed intake, egg production, egg mass, body weight, percentage egg yolk, and yolk/albumen ratio than Dekalb White. Bovans White had significantly lower feed conversion, egg weight, egg specific gravity, percentage of albumen weight, percentage of shell weight, and Haugh unit than Dekalb White. When dietary energy increased from 2,719 to 2,956 kcal of ME/kg, hens adjusted feed intake from 107.6 to 101.1 g/hen per day to achieve a constant energy intake so that the same amount of dietary energy (5.8 kcal) was used to produce 1 g of egg. Increasing dietary energy by the addition of poultry oil increased early egg weight, which was mostly due to increased yolk weight. Increasing dietary energy by addition of poultry oil significantly decreased feed conversion and egg specific gravity but had no effect on egg production, egg mass, body weight, or mortality. Increasing dietary energy by addition of poultry oil to a ratio of 282 kcal of ME/g lysine maximized egg weight during phase I. The energy per lysine ratio required for optimal profits varied with egg price and feed ingredient prices, which were variable.

Animal Feed↗
PubMed2005

Effects of beta-mannanase in corn-soy diets on commercial leghorns in second-cycle hens.

beta-Mannanase (Hemicell) is a unique enzyme-based feed ingredient that can hydrolyze beta-mannan, an antinutritional fiber in feed. Because soybean meal contains beta-mannan and its derivatives, addition of beta-mannanase may improve soybean-meal utilization. The purpose of this study was to evaluate the effect of beta-mannanase on performance of commercial Leghorns fed corn-soybean meal based diets. In this experiment, 3 diets were formulated. The metabolizable energy content for diet 1 (high-energy diet) was 2,951 kcal/kg, which was 120 kcal/kg higher than diet 2 (low-energy diet supplemented with beta-mannanase) and diet 3 (low-energy diet without beta-mannanase). Hy-Line W-36 hens (n = 720, 98 wk old) were randomly divided into 3 dietary treatments (16 replicates of 15 hens per treatment). The trial lasted for 12 wk. Overall average feed conversion of hens fed the low-energy diet supplemented with beta-mannanase was similar to that of hens fed the high-energy diet, and both were significantly lower than that of hens fed the low-energy diet without beta-mannanase. There were no significant differences in overall average egg production and egg mass among 3 dietary treatments for the 12-wk period. However, the addition of beta-mannanase significantly increased average egg production and egg mass of hens fed the low-energy diet from wk 5 to 8. There were no significant differences in feed intake, egg specific gravity, egg weight, mortality, body weight, and body weight variability among the 3 dietary treatments. beta-Mannanase supplementation improved energy utilization of corn-soybean layer diets and has potential to reduce the cost of practical laying hen diets containing beta-mannan.

Animal Feed↗
PubMed2005

PET detection of solitary distant skeletal muscle metastasis of esophageal adenocarcinoma.

A 67-year-old man with progressive dysphagia was recently diagnosed with a gastroesophageal junction adenocarcinoma. Contrast-enhanced CT scans of the abdomen and pelvis reported a large GE junction tumor without evidence of metastatic disease. FDG positron emission tomography revealed intense tracer accumulation in the soft tissue mass at the GE junction consistent with the primary neoplasm. In addition, PET scan also identified a solitary focus of intense FDG accumulation at the musculotendinous junction of the right gluteus minimus muscle. Subsequent MRI demonstrated mild enhancement and could not differentiate between tumor versus inflammation. Needle biopsy was performed and confirmed metastatic esophageal adenocarcinoma. A case of skeletal muscle metastases from late-stage (IV) gastroesophageal adenocarcinoma was previously reported. However, a solitary metastasis to a distant skeletal muscle without evidence of other lymphatic and hematogenous metastasis is quite unusual. The case supports the previous report that PET is superior in detecting distant metastases for initial staging of esophageal carcinoma over CT.

Adenocarcinoma↗