bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of CDC2/CyclinB1 in gliomas, and CDC2 depletion inhibits proliferation of human glioma cells in vitro and in vivo
Authors: Chen Hua , Huang Qiang , Dong Jun , Zhai De-Zhong , Wang Ai-Dong , Lan Qing 
Published: January 2008

Abstract

Background
Gliomas are the most common and aggressive primary brain tumors for which unfortunately no effective treatment modalities exist despite advances in molecular biology as the knowledge base to unravel the extremely complex molecular mechanisms of tumorigenesis is limited. In this study an attempt has been made to understand the molecular pathological basis of tumorigenesis which led to an identification of an oncogene, CDC2, and an epigenetic strategy has been evaluated to control the tumorigensis by downregulating this oncogene.

Methods
Tissue microarrays were utilized to investigate the expression of genes in a large number of tumor samples and to identify overexpressed genes which could be potentially causing tumorigenesis. Retroviral vectors expressing short hairpin RNAs (shRNAs) targeted against CDC2 were designed and transducted into human glioma cell line ex vivo in order to downregulate the expression of CDC2. Real-Time PCR was used to determine the level of CDC2 mRNA. Western Blotting was used to determine the level of expression of CDC2 protein as measure to quantify down regulation of CDC2 expression along with use of flow cytometry to investigate effect of shRNAs on cell cycles and detection of apoptosis. Following ex vivo study, viral particles containing small interfering RNA for CDC2 were subsequently injected into xenogeneic graft tumor of nude mice and the weight of human glioma xenografts, survival and resulting phenotypic changes of target gene were investigated.

Results
Human glioma tissue microarrays indicated the positive expression rates of CDC2/CyclinB1 with a positive correlation with pathologic grades (r = 0.982, r = 0.959, respectively). Retroviral vectors expressing short hairpin RNAs (shRNAs) against CDC2 caused efficient deletion of CDC2, cellular G2/M arrest concluding in apoptosis and inhibition of proliferation in human glioma cells U251 and SHG-44 cell lines ex vivo. And the viral particles containing small interfering RNA for CDC2 were subsequently injected into subcutaneous and intracranial xenogeneic graft tuomrs of nude mice. For subcutaneous tumors, injection of CDC2-shRNA retroviruses significantly decreased tumor weight and volume compared with control. Immunohistochemistry indicated that CDC2 are negative and TUNEL are positive in tumors treated with recombinant retrovirus. For mice implanted with intracranial gliomas, treatment of CDC2-shRNA retroviruses increased survival times compared with control.

Conclusion
CDC2 gene plays an important role in the proliferation of human gliomas. Downregulation of CDC2 could potentialy inhibit human gliomas cells growth ex vivo and in vivo. From these results, it was suggested that CDC2 might be a potential target on gene therapy of human gliomas.
Efficient display of active lipase LipB52 with a Pichia pastoris cell surface display system and comparison with the LipB52 displayed on Saccharomyces cerevisiae cell surface
Authors: Jiang Zhengbing , Gao Bei , Ren Ren , Tao Xingyi , Ma Yushu , Wei Dongzhi 
Published: January 2008

Abstract

Background
For industrial bioconversion processes, the utilization of surface-displayed lipase in the form of whole-cell biocatalysts is more advantageous, because the enzymes are displayed on the cell surface spontaneously, regarded as immobilized enzymes.

Results
Two Pichia pastoris cell surface display vectors based on the flocculation functional domain of FLO with its own secretion signal sequence or the α-factor secretion signal sequence were constructed respectively. The lipase gene lipB52 fused with the FLO gene was successfully transformed into Pichia pastoris KM71. The lipase LipB52 was expressed under the control of the AOX1 promoter and displayed on Pichia pastoris KM71 cell surface with the two Pichia pastoris cell surface display vectors. Localization of the displayed LipB52 on the cell surface was confirmed by the confocal laser scanning microscopy (CLSM). The LipB52 displayed on the Pichia pastoris cell surface exhibited activity toward p-nitrophenol ester with carbon chain length ranging from C10 to C18, and the optimum substrate was p-nitrophenol-caprate (C10), which was consistent with it displayed on the Saccharomyces cerevisiae EBY100 cell surface. The hydrolysis activity of lipase LipB52 displayed on Pichia pastoris KM71-pLHJ047 and KM71-pLHJ048 cell surface reached 94 and 91 U/g dry cell, respectively. The optimum temperature of the displayed lipases was 40°C at pH8.0, they retained over 90% activity after incubation at 60°C for 2 hours at pH 7.0, and still retained 85% activity after incubation for 3 hours.

Conclusion
The LipB52 displayed on the Pichia pastoris cell surface exhibited better stability than the lipase LipB52 displayed on Saccharomyces cerevisiae cell surface. The displayed lipases exhibited similar transesterification activity. But the Pichia pastoris dry cell weight per liter (DCW/L) ferment culture was about 5 times than Saccharomyces cerevisiae, the lipase displayed on Pichia pastoris are more suitable for whole-cell biocatalysts than that displayed on Saccharomyces cerevisiae cell surface.
Clinical peripherality: development of a peripherality index for rural health services
Authors: Swan Gillian M , Selvaraj Sivasubramaniam , Godden David J 
Published: January 2008

Abstract

Background
The configuration of rural health services is influenced by geography. Rural health practitioners provide a broader range of services to smaller populations scattered over wider areas or more difficult terrain than their urban counterparts. This has implications for training and quality assurance of outcomes. This exploratory study describes the development of a "clinical peripherality" indicator that has potential application to remote and rural general practice communities for planning and research purposes.

Methods
Profiles of general practice communities in Scotland were created from a variety of public data sources. Four candidate variables were chosen that described demographic and geographic characteristics of each practice: population density, number of patients on the practice list, travel time to nearest specialist led hospital and travel time to Health Board administrative headquarters. A clinical peripherality index, based on these variables, was derived using factor analysis. Relationships between the clinical peripherality index and services offered by the practices and the staff profile of the practices were explored in a series of univariate analyses.

Results
Factor analysis on the four candidate variables yielded a robust one-factor solution explaining 75% variance with factor loadings ranging from 0.83 to 0.89. Rural and remote areas had higher median values and a greater scatter of clinical peripherality indices among their practices than an urban comparison area. The range of services offered and the profile of staffing of practices was associated with the peripherality index.

Conclusion
Clinical peripherality is determined by the nature of the practice and its location relative to secondary care and administrative and educational facilities. It has features of both gravity model-based and travel time/accessibility indicators and has the potential to be applied to training of staff for rural and remote locations and to other aspects of health policy and planning. It may assist planners in conceptualising the effects on general practices of centralising specialist clinical services or administrative and educational facilities.
Maternal peripheral blood level of IL-10 as a marker for inflammatory placental malaria
Authors: Kabyemela Edward R , Muehlenbachs Atis , Fried Michal , Kurtis Jonathan D , Mutabingwa Theonest K , Duffy Patrick E 
Published: January 2008

AbstractBackgroundPlacental malaria (PM) is an important cause of maternal and foetal mortality in tropical areas, and severe sequelae and mortality are related to inflammation in the placenta. Diagnosis is difficult because PM is often asymptomatic, peripheral blood smear examination detects parasitemia as few as half of PM cases, and no peripheral markers have been validated for placental inflammation.MethodsIn a cohort of Tanzanian parturients, PM was determined by placental blood smears and placental inflammation was assessed by histology and TNF mRNA levels. Maternal peripheral blood levels of several immune mediators previously implicated in PM pathogenesis, as well as ferritin and leptin were measured. The relationship between the levels of these soluble factors to PM and placental inflammation was examined.ResultsPeripheral levels of TNF, TNF-RI, TNF-RII, IL-1, IL-10, and ferritin were elevated during PM, whereas levels of IFN-γ, IL-4, IL-5 and IL-6 were unchanged and levels of leptin were decreased. In receiver operating characteristic curve analysis, IL-10 had the greatest area under the curve, and would provide a sensitivity of 60% with a false positive rate of 10%. At a cut off level of 15 pg/mL, IL-10 would detect PM with a sensitivity of 79.5% and a specificity of 84.3%. IL-10 levels correlated with placental inflammatory cells and placental TNF mRNA levels in first time mothers.ConclusionThese data suggest that IL-10 may have utility as a biomarker for inflammatory PM in research studies, but that additional biomarkers may be required to improve clinical diagnosis and management of malaria during pregnancy.
Relationships of low serum vitamin D3with anthropometry and markers of the metabolic syndrome and diabetes in overweight and obesity
Authors: McGill Anne-Thea , Stewart Joanna M , Lithander Fiona E , Strik Caroline M , Poppitt Sally D 
Published: January 2008

AbstractLow serum 25 hydroxyvitamin D3 (vitamin D3) is known to perturb cellular function in many tissues, including the endocrine pancreas, which are involved in obesity and type II diabetes mellitus (TIIDM). Vitamin D3 insufficiency has been linked to obesity, whether obesity is assessed by body mass index (BMI) or waist circumference (waist). Central obesity, using waist as the surrogate, is associated with the metabolic syndrome (MetSyn), insulin resistance, TIIDM and atherosclerotic cardiovascular disease (CVD). We tested how vitamin D3 was related to measures of fat mass, MetSyn markers, haemoglobin A1c (HbA1c) and MetSyn in a cross-sectional sample of 250 overweight and obese adults of different ethnicities. There were modest inverse associations of vitamin D3 with body weight (weight) (r = -0.21, p = 0.0009), BMI (r = -0.18, p = 0.005), waist (r = -0.14, p = 0.03), [but not body fat % (r = -0.08, p = 0.24)], and HbA1c (r = -0.16, p = 0.01). Multivariable regression carried out separately for BMI and waist showed a decrease of 0.74 nmol/L (p = 0.002) in vitamin D3 per 1 kg/m2 increase in BMI and a decrease of 0.29 nmol/L (p = 0.01) per 1 cm increase in waist, with each explaining approximately 3% of the variation in vitamin D3 over and above gender, age, ethnicity and season.The similar relationships of BMI and waist with vitamin D3 may have been due to associations between BMI and waist, or coincidental, where different mechanisms relating hypovitaminosis D3 to obesity occur concurrently. Previously reviewed mechanisms include that 1) low vitamin D3, may impair insulin action, glucose metabolism and various other metabolic processes in adipose and lean tissue 2) fat soluble-vitamin D3 is sequestered in the large adipose compartment, and low in serum, 3) obese people may be sensitive about their body shape, minimising their skin exposure to view and sunlight (not tested). We showed evidence for the first theory but no evidence to support the second.In the current study, serum vitamin D3 was inversely related to weight, BMI and markers of TIIDM (large waist, raised HbA1c) but not to adipose mass nor to MetSyn per se.
Curcumin sensitizes TRAIL-resistant xenografts: molecular mechanisms of apoptosis, metastasis and angiogenesis
Authors: Shankar Sharmila , Ganapathy Suthakar , Chen Qinghe , Srivastava Rakesh K 
Published: January 2008

AbstractBackgroundWe have recently shown that curcumin (a diferuloylmethane, the yellow pigment in turmeric) enhances apoptosis-inducing potential of TRAIL in prostate cancer PC-3 cells, and sensitizes TRAIL-resistant LNCaP cellsin vitrothrough multiple mechanisms. The objectives of this study were to investigate the molecular mechanisms by which curcumin sensitized TRAIL-resistant LNCaP xenograftsin vivo.MethodsProstate cancer TRAIL-resistant LNCaP cells were implanted in Balb c nude mice to examine the effects of curcumin and/or TRAIL on tumor growth and genes related to apoptosis, metastasis and angiogenesis.ResultsCurcumin inhibited growth of LNCaP xenografts in nude mice by inducing apoptosis (TUNEL staining) and inhibiting proliferation (PCNA and Ki67 staining), and sensitized these tumors to undergo apoptosis by TRAIL. In xenogrfated tumors, curcumin upregulated the expression of TRAIL-R1/DR4, TRAIL-R2/DR5, Bax, Bak, p21/WAF1, and p27/KIP1, and inhibited the activation of NFκB and its gene products such as cyclin D1, VEGF, uPA, MMP-2, MMP-9, Bcl-2 and Bcl-XL. The regulation of death receptors and members of Bcl-2 family, and inactivation of NFκB may sensitize TRAIL-resistant LNCaP xenografts. Curcumin also inhibited number of blood vessels in tumors, and circulating endothelial growth factor receptor 2-positive endothelial cells in mice.ConclusionThe ability of curcumin to inhibit tumor growth, metastasis and angiogenesis, and enhance the therapeutic potential of TRAIL suggests that curcumin alone or in combination with TRAIL can be used for prostate cancer prevention and/or therapy.
The influence of physical activity and yoga on central arterial stiffness
Authors: Duren Courtney M , Cress Marie E , McCully Kevin K 
Published: January 2008

Abstract

Purpose
Central arterial stiffness is an accepted risk factor for cardiovascular disease. While aerobic activity is associated with reduced stiffness the influence of practicing yoga is unknown. The aims of this study were to: 1) evaluate arterial stiffness in middle-aged adults who regularly practiced yoga, performed regular exercise, or were inactive, 2) evaluate the reproducibility of arterial stiffness measured in the left and right carotid artery and by pulse wave velocity (PWV).

Methods
Twenty six healthy subjects (male and female, 40–65 yrs old) were tested on two separate days. Carotid artery distensibility (DC) was measured with ultrasound. Physical activity was determined by questionnaire.

Results
Yoga and aerobic subjects had similar physical activity levels. Yoga and aerobic groups were not different in either DC (p = 0.26) or PWV (p = 0.21). The sedentary group had lower DC and higher PWV compared to the aerobic and yoga groups (both, p < 0.001). Stiffness measures were reliable day to day (coefficients of variation ~2.5%) and similar between left and right arteries (CV = 2.2%).

Conclusion
Physical activity was a strong predictor of both measures of arterial stiffness, although other factors such as nutritional status need to be accounted for. An independent effect of practicing yoga could not be detected. Stiffness measures were reproducible and left and right sides were consistent with each other.
Laparotomy enables retrograde dilatation and stent placement for malignant esophago-respiratory fistula
Authors: Rehders Alexander , Cupisti Kenko , Schmitt Marcus , Renter Marc A , Kröpil Patrick , Iskender Özcan , Knoefel Wolfram T 
Published: January 2008

Abstract

Background
Malignant esophageal stenosis with complete obstruction and esophagorespiratory fistula (ERF) is difficult to treat with standard endoscopic techniques.

Case presentation
We report a patient in whom with local recurrence of esophageal carcinoma an esophagotracheal fistula occurred. Initially the patient had undergone esophageal resection with interposition of a gastric tube. Due to complete obstruction of the lumen by recurrent tumor conventional transoral stent placement failed. For retrograde dilatation a laparotomy was performed. Via a duodenal incision endoscopic access to the gastric tube was achieved. Using a guidewire the esophageal obstruction was traversed and dilated. Then it was possible to place an esophageal stent via an antegrade approach.

Conclusion
Open surgery enables a safe access for retrograde endoscopic therapy in patients who had undergone esophageal resection with gastric interposition.
Does prior acute exercise affect postexercise substrate oxidation in response to a high carbohydrate meal?
Authors: Long Wiley , Wells Katherine , Englert Virginia , Schmidt Stacy , Hickey Matthew S , Melby Christopher L 
Published: January 2008

Abstract

Background
Consumption of a mixed meal increases postprandial carbohydrate utilization and decreases fat oxidation. On the other hand, acute endurance exercise increases fat oxidation and decreases carbohydrate utilization during the post-exercise recovery period. It is possible that the resulting post-exercise increase in circulating nonesterified fatty acids could attenuate the ability of ingested carbohydrate to inhibit lipid oxidation. The purpose of this study was to determine whether prior exercise attenuates the usual meal-induced decline in lipid oxidation.

Methods
Six healthy, physically active young subjects (x age = 26.3 years, 4 males, 2 females) completed three treatments in random order after a ~10 h fast: (a) Exercise/Carbohydrate (Ex/CHO) – subjects completed a bout of exercise at 70% VO2peak (targeted net energy cost of 400 kcals), followed by consumption of a carbohydrate-rich meal; (b) Exercise/Placebo (Ex/Placebo) – subjects completed an identical bout of exercise followed by consumption of a placebo; and (c) No Exercise/Carbohydrate (NoEx/CHO) – subjects sat quietly rather than exercising and then consumed the carbohydrate-rich meal. Blood samples were obtained before and during the postprandial period to determine plasma glucose, insulin, and non-esterified fatty acids (NEFA). Respiratory gas exchange measures were used to estimate rates of fat and carbohydrate oxidation.

Results
Plasma NEFA were approximately two-fold higher immediately following the two exercise conditions compared to the no-exercise condition, while meal consumption significantly increased insulin and glucose in both Ex/CHO and NoEx/CHO. NEFA concentrations fell rapidly during the 2-h postprandial period, but remained higher compared to the NoEx/CHO treatment. Carbohydrate oxidation increased rapidly and fat oxidation decreased in response to the meal, with no differences in the rates of carbohydrate and fat oxidation during recovery between the Ex/CHO and NoEx/CHO conditions.

Conclusion
The plasma NEFA concentration is increased during the post exercise period, which is associated with elevated fat oxidation when no meal is consumed. However, when a mixed meal is consumed immediately following exercise, the initially elevated plasma NEFA concentration decreases rapidly, and postexercise fat oxidation during this 2-h postexercise, postprandial period is no higher than that of the 2-h postprandial period without prior exercise.
Late Cardiac Effects of Adjuvant Chemotherapy in Breast Cancer Survivors Treated on Southwest Oncology Group Protocol S8897
Authors: Ganz Patricia A. , Hussey Michael A. , Moinpour Carol M. , Unger Joseph M. , Hutchins Laura F. , Dakhil Shaker R. , Giguere Jeffrey K. , Goodwin J. Wendall , Martino Silvana , Albain Kathy S. 
Published: January 2008

Purpose The late cardiac effects of adjuvant anthracycline therapy in survivors of early-stage breast cancer have had limited study. Subclinical and clinical cardiac late effects may contribute to added comorbidity over time. Patients and Methods We recruited patients treated on Southwest Oncology Group (SWOG) protocol S8897 who had been randomly assigned to adjuvant chemotherapy with or without doxorubicin. Left ventricular ejection fraction (LVEF) was evaluated at 5 to 8 years and 10 to 13 years after treatment randomization. Cardiac risk factors and events were reported by clinicians annually between the two assessments. Results A total of 180 breast cancer survivors from a potential sample of 1,176 patients were entered, 163 patients at 5 to 8 years and 17 additional patients at 10 to 13 years, with 93 longitudinal assessments of LVEF. There was no significant difference in the proportion of women with an LVEF less than 50% at 5 to 8 (cyclophosphamide, doxorubicin, and fluorouracil [CAF] v cyclophosphamide, methotrexate, and fluorouracil [CMF]: 5% v 7%; P = .68) or 10 to 13 years (CAF v CMF: 3% v 0%; P = .16); however, in an exploratory analysis, the mean LVEF in the doxorubicin group was statistically significantly lower in the 5- to 8-year sample (64.8% v 61.4%; P = .01) but not in the 10- to 13-year sample. In the longitudinal analysis, there was no significant deterioration in LVEF. Conclusion Women enrolled onto an adjuvant chemotherapy treatment clinical trial for breast cancer were successfully recruited to participate in a research study of the late effects of treatment, although many SWOG institutions and potentially eligible patients chose not to participate. In this selected sample, with up to 13 years of follow-up, exposure to doxorubicin did not increase the likelihood of adverse cardiac effects.
Relationship Between Quantitative Estrogen and Progesterone Receptor Expression and Human Epidermal Growth Factor Receptor 2 (HER-2) Status With Recurrence in the Arimidex, Tamoxifen, Alone or in Combination Trial
Authors: Dowsett Mitch , Allred Craig , Knox Jill , Quinn Emma , Salter Janine , Wale Chris , Cuzick Jack , Houghton Joan , Williams Norman , Mallon Elizabeth , Bishop Hugh , Ellis Ian , Larsimont Denis , Sasano Hironobu , Carder Pauline , Cussac Antonio Llombart , Knox Fiona , Speirs Valerie , Forbes John , Buzdar Aman 
Published: January 2008

Purpose To determine the relationship between quantitative estrogen-receptor (ER) and progesterone-receptor (PgR) expression and human epidermal growth factor 2 (HER-2) status with time to recurrence (TTR) in postmenopausal women with hormone receptor–positive primary breast cancer treated with anastrozole or tamoxifen as adjuvant therapy. Patients and Methods Formalin-fixed, paraffin-embedded tumor blocks were retrospectively collected from patients in the monotherapy arms of the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial and centrally tested for ER, PgR and HER-2. ER and PgR were scored using continuous scales and HER-2 was scored as 0 to 3+ with 2+ cases being analyzed by fluorescence in situ hybridization. Results Blocks were collected from 2,006 of 5,880 eligible patients. Tissue was assessable and ER and/or PgR positivity confirmed centrally in 1,782 cases. In these, TTR was longer for anastrozole than for tamoxifen by a similar extent to that in the overall trial. None of the three biomarkers identified a set of patients with differential benefit from anastrozole over tamoxifen. Patients with low ER, low PgR, and high HER-2 expression had a poorer prognosis with either drug. Only 2.6% of patients in the highest quartile of PgR experienced recurrence after 5 years, compared with 13.2% in the lowest quartile. Conclusion Quantitative expression of ER and PgR and HER-2 status did not identify patients with differential relative benefit from anastrozole over tamoxifen: TTR was longer for anastrozole than for tamoxifen in all molecular subgroups. Low ER or PgR or high HER-2 expression are associated with a high risk of recurrence with either anastrozole or tamoxifen.