bluuebunny/crossref_metadata_2025 huggingface dataset:
Ability of Lactobacillus fermentum to overcome host α-galactosidase deficiency, as evidenced by reduction of hydrogen excretion in rats consuming soya α-galacto-oligosaccharides
Authors: LeBlanc Jean Guy , Ledue-Clier Florence , Bensaada Martine , de Giori Graciela Savoy , Guerekobaya Theodora , Sesma Fernando , Juillard Vincent , Rabot Sylvie , Piard Jean-Christophe
Published: January 2008

Background

Soya and its derivatives represent nutritionally high quality food products whose major drawback is their high content of α-galacto-oligosaccharides. These are not digested in the small intestine due to the natural absence of tissular α-galactosidase in mammals. The passage of these carbohydrates to the large intestine makes them available for fermentation by gas-producing bacteria leading to intestinal flatulence. The aim of the work reported here was to assess the ability of α-galactosidase-producing lactobacilli to improve the digestibility of α-galacto-oligosaccharidesin situ.

Results

Gnotobiotic rats were orally fed with soy milk and placed in respiratory chambers designed to monitor fermentative gas excretion. The validity of the animal model was first checked using gnotobiotic rats monoassociated with aClostridium butyricumhydrogen (H2)-producing strain. Ingestion of native soy milk by these rats caused significant H2emission while ingestion of α-galacto-oligosaccharide-free soy milk did not, thus validating the experimental system. When native soy milk was fermented using the α-galactosidase-producingLactobacillus fermentumCRL722 strain, the resulting product failed to induce H2emission in rats thus validating the bacterial model. WhenL. fermentumCRL722 was coadministered with native soy milk, a significant reduction (50 %,P= 0.019) in H2emission was observed, showing that α-galactosidase fromL. fermentumCRL722 remained activein situ, in the gastrointestinal tract of rats monoassociated withC. butyricum. In human-microbiota associated rats,L. fermentumCRL722 also induced a significant reduction of H2emission (70 %,P= 0.004).

Conclusion

These results strongly suggest thatL. fermentumα-galactosidase is able to partially alleviate α-galactosidase deficiency in rats. This offers interesting perspectives in various applications in which lactic acid bacteria could be used as a vector for delivery of digestive enzymes in man and animals.
In vitro activity of telithromycin against Haemophilus influenzae at epithelial lining fluid concentrations
Authors: De Vecchi Elena , Nicola Lucia , Larosa Monica , Drago Lorenzo
Published: January 2008

Background

Haemophilus influenzae is one of the main aetiological agents of community-acquired respiratory tract infections. The primary aim of this study was to evaluate the antibacterial activity of telithromycin against H. influenzae clinical isolates showing different pattern of resistance in comparison with azithromycin and clarithromycin at 1/4 ×, 1/2 ×, 1 ×, 2 ×, 4 × minimum inhibitory concentration (MIC) and to peak concentrations in epithelial lining fluid (ELF). The secondary aim was to determine the influence of CO2 enriched atmosphere on bacterial susceptibility.

Results

Telithromycin showed high activity against H. influenzae, including strains susceptible to β-lactams (n = 200), β-lactamase producer (n = 50) and β-lactamase negative ampicillin resistant (BLNAR) (n = 10), with MIC from ≤0.03 to 4 mg/L, and MIC50/MIC90 of 1/2 mg/L with susceptibility rate of 100%, and minimum bactericidal concentrations (MBC) from 2 to 4-fold higher than the MIC. Azithromycin was the most active tested macrolide (range: 0.25 – 4 mg/L; MIC50/MIC90: 1/2 mg/L), comparable to telithromycin, while clarithromycin showed the highest MICs and MBCs (range: 0.25 – 8 mg/L; MIC50/MIC90: 2/8 mg/L). In time-kill studies, telithromycin showed a bactericidal activity at the higher concentrations (4 – 2 × MIC and ELF) against all the strains, being complete after 12 – 24 hours from drug exposition. At MIC concentrations, at ambient air, bactericidal activity of telithromycin and azithromycin was quite similar at 12 hours, and better than that of clarithromycin. Besides, telithromycin and clarithromycin at ELF concentrations were bactericidal after 12 hours of incubation for most strains, while 24 hours were needed to azithromycin to be bactericidal. Incubation in CO2 significantly influenced the MICs and MBCs, and only slightly the in vitro killing curves.

Conclusion

Telithromycin showed an in-vitro potency against H. influenzae comparable to azithromycin, with an in-vitro killing rate more rapid and superior to clarithromycin at 2X-MIC against β-lactamase producers and BLNAR strains, and to azithromycin at ELF concentrations against β-lactamase negative strains. Against all strains, MICs and MBCs were lower in the absence of CO2 for the tested antibiotics, showing an adverse effect of incubation in a CO2 environment. The in-vitro potency together with the tissue concentrations of the antimicrobial, should be considered in predicting efficacy.
Frequent expression loss of Inter-alpha-trypsin inhibitor heavy chain (ITIH) genes in multiple human solid tumors: A systematic expression analysis
Authors: Hamm Alexander , Veeck Juergen , Bektas Nuran , Wild Peter J , Hartmann Arndt , Heindrichs Uwe , Kristiansen Glen , Werbowetski-Ogilvie Tamra , Del Maestro Rolando , Knuechel Ruth , Dahl Edgar
Published: January 2008

Background

The inter-alpha-trypsin inhibitors (ITI) are a family of plasma protease inhibitors, assembled from a light chain – bikunin, encoded byAMBP– and five homologous heavy chains (encoded byITIH1,ITIH2,ITIH3,ITIH4, andITIH5), contributing to extracellular matrix stability by covalent linkage to hyaluronan. So far, ITIH molecules have been shown to play a particularly important role in inflammation and carcinogenesis.

Methods

We systematically investigated differential gene expression of theITIHgene family, as well asAMBPand the interacting partnerTNFAIP6in 13 different human tumor entities (of breast, endometrium, ovary, cervix, stomach, small intestine, colon, rectum, lung, thyroid, prostate, kidney, and pancreas) using cDNA dot blot analysis (Cancer Profiling Array, CPA), semiquantitative RT-PCR and immunohistochemistry.

Results

We found thatITIHgenes are clearly downregulated in multiple human solid tumors, including breast, colon and lung cancer. Thus,ITIHgenes may represent a family of putative tumor suppressor genes that should be analyzed in greater detail in the future. For an initial detailed analysis we choseITIH2expression in human breast cancer. Loss ofITIH2expression in 70% of cases (n = 50, CPA) could be confirmed by real-time PCR in an additional set of breast cancers (n = 36). Next we studied ITIH2 expression on the protein level by analyzing a comprehensive tissue micro array including 185 invasive breast cancer specimens. We found a strong correlation (p < 0.001) between ITIH2 expression and estrogen receptor (ER) expression indicating that ER may be involved in the regulation of this ECM molecule.

Conclusion

Altogether, this is the first systematic analysis on the differential expression ofITIHgenes in human cancer, showing frequent downregulation that may be associated with initiation and/or progression of these malignancies.
Markers of subtypes in inflammatory breast cancer studied by immunohistochemistry: Prominent expression of P-cadherin
Authors: Ben Hamida Azza , Labidi Intidhar S , Mrad Karima , Charafe-Jauffret Emmanuelle , Ben Arab Saïda , Esterni Benjamin , Xerri Luc , Viens Patrice , Bertucci François , Birnbaum Daniel , Jacquemier Jocelyne
Published: January 2008

Background

Inflammatory breast cancer (IBC) is a distinct and aggressive form of locally-advanced breast cancer with high metastatic potential. In Tunisia, IBC is associated with a high death rate. Among the major molecular subtypes, basal breast carcinomas are poorly differentiated, have metastatic potential and poor prognosis, but respond relatively well to chemotherapy. The aim of this study was to determine the distribution of molecular subtypes in IBC and identify factors that may explain the poor prognosis of IBC.

Methods

To determine breast cancer subtypes we studied by immunohistochemistry the expression of 12 proteins in a series of 91 Tunisian IBC and 541 non-IBC deposited in tissue microarrays.

Results

We considered infiltrating ductal cases only. We found 33.8% of basal cases in IBC vs 15.9% in non-IBC (p < 0.001), 33.3% of ERBB2-overexpressing cases in IBC vs 14.5% in non-IBC (p < 0.001), and 29.3% of luminal cases in IBC vs 59.9% in non-IBC (p < 0.001). The most differentially-expressed protein between IBCs and non-IBCs was P-cadherin. P-cadherin expression was found in 75.9% of all IBC vs 48.2% of all non-IBC (p < 0.001), 95% of IBC vs 69% of non-IBC (p = 0.02) in basal cases, and 82% of IBC vs 43% of non-IBC (p < 0.001) in luminal cases. Logistic regression determined that the most discriminating markers between IBCs and non-IBCs were P-cadherin (OR = 4.9, p = 0.0019) MIB1 (OR = 3.6, p = 0.001), CK14 (OR = 2.7, p = 0.02), and ERBB2 (OR = 2.3, p = 0.06).

Conclusion

Tunisian IBCs are characterized by frequent basal and ERBB2 phenotypes. Surprisingly, luminal IBC also express the basal marker P-cadherin. This profile suggests a specificity that needs further investigation.
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

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

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

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

Background

Placental 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.

Methods

In 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.

Results

Peripheral 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.

Conclusion

These 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

Low 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

Background

We 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.

Methods

Prostate 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.

Results

Curcumin 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.

Conclusion

The 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

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

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

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.
The Prognostic Significance of Patient-Reported Outcomes in Cancer Clinical Trials
Authors: Gotay Carolyn C. , Kawamoto Crissy T. , Bottomley Andrew , Efficace Fabio
Published: January 2008

Purpose

Patient-reported outcomes (PROs), routinely collected as a part of cancer clinical trials, have been linked with survival in numerous clinical studies, but a comprehensive critical review has not been reported. This study systematically assessed the impact of PROs on patient survival after a cancer diagnosis within the context of clinical trials.

Design

Cancer clinical trials that assessed baseline PROs and mortality were identified through MEDLINE (through December 2006) supplemented by the Cochrane database, American Society of Clinical Oncology/European Society for Medical Oncology abstracts and hand searches. Inclusion criteria were publication in English language and use of multivariate analyses of PROs that controlled for one or more clinical factors. Two raters reviewed each study, abstracted data, and assessed study quality; two additional raters verified abstractions.

Results

In 36 of 39 studies (N = 13,874), at least one PRO was significantly associated with survival (P < .05) in multivariate analysis, with varying effect sizes. Studies of lung (n = 12) and breast cancer (n = 8) were most prevalent. The most commonly assessed PRO was quality of life, measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 in 56% of studies. Clinical variables adjusted for included performance status (PS), treatment arm, stage, weight loss, and serum markers. Results indicated that PROs provide distinct prognostic information beyond standard clinical measures in cancer clinical trials.

Conclusion

PROs might be considered for stratification purposes in future trials, as they were often better predictors of survival than PS. Studies are needed to determine whether interventions that improve PROs also increase survival and to identify explanatory mechanisms through which PROs relate to survival.
Differential loss of histone H3 isoforms mono-, di- and tri-methylated at lysine 4 during X-inactivation in female embryonic stem cells
Authors: O'Neill Laura P. , Spotswood Hugh T. , Fernando Milan , Turner Bryan M.
Published: January 2008

Silencing of genes on one of the two female X chromosomes early in development helps balance expression of X-linked genes between XX females and XY males and involves chromosome-wide changes in histone variants and modifications. Mouse female embryonic stem (ES) cells have two active Xs, one of which is silenced on differentiation, and provide a powerful model for studying the dynamics of X inactivation. Here, we use immunofluorescence microscopy of metaphase chromosomes to study changes in H3 mono-, di- or tri-methylated at lysine 4 (H3K4me1, -2 or -3) on the inactivating X (Xi) in female ES cells. H3K4me3 is absent from Xi in approximately 25% of chromosome spreads by day 2 of differentiation and in 40–50% of spreads by days 4–6, making it one of the earliest detectable changes on Xi. In contrast, loss of H3K4me2 occurs 1–2 days later, when histone acetylation also diminishes. Remarkably, H3K4me1 is depleted on both (active) X chromosomes in undifferentiated female ES cells, and on the single X in males, and remains depleted on Xi. Consistent with this, chromatin immunoprecipitation reveals differentiation-related reductions in H3K4me2 and H3K4me3 at the promoter regions of genes undergoing X-inactivation in female ES cells, but no comparable change in H3K4me1.
Within-plant variation in palatability and chemical defenses in the green seaweed Avrainvillea elliottii
Authors: Lima Leonardo Martha de S. , Alor Rosemarie , Uriostegui Ricardo , Murray Steven N. , Pereira Renato C.
Published: January 2008

This study tested potential chemical defense of the green seaweed Avrainvillea elliottii against grazing by the sea urchin Lytechinus variegatus. We examined intraspecific variation of defensive chemicals in different parts of the thallus (margin, blade and stipe). We predicted that thallus parts making the greatest contributions to thallus fitness would show the greatest chemical deterrence to herbivory. The susceptibility of the whole alga and its different parts to consumption by L. variegatus was evaluated using assays consisting of powdered algae treated with natural concentrations of crude A. elliottii extract. Results from feeding evaluations showed that the crude extracts of whole plants and different thallus parts deterred consumption by this sea urchin. The results also supported our prediction that stronger chemical defenses occur in the more apical and younger areas of the thallus (margins), parts whose loss would result in the greatest reduction of fitness. These results provide added evidence supporting the ability of siphonaceous or coenocytic green macroalgae to concentrate defensive chemicals in growing parts.
Nanoflagellates from coastal waters of southern Brazil (32°S)
Authors: Bergesch Marli , Odebrecht Clarisse , Moestrup Øjvind
Published: January 2008

A taxonomic survey of nanoflagellates in the extreme southern Brazilian coastal waters of the Patos Lagoon estuary and adjacent coastal shelf was undertaken using transmission electron microscopy. A total of 44 species was recorded including 42 nanoflagellates, one scale-bearing amoeba and two species incertae sedis. Scale-bearing haptophytes predominated (27 species), followed by prasinophytes (7), chrysophytes (6), pedinellids (2), incertae sedis (2) and one scale-bearing amoeba. Most of the species (42) are new records for Brazilian marine waters. Among the haptophytes, Chrysochromulina was the most species-rich genus, occurring mainly in high salinity waters, and C. simplex was the most frequent species. Scales of undescribed Chrysochromulina species were observed and documented. Other haptophytes present were Prymnesium parvum and Phaeocystis scrobiculata. Five scale-bearing prasinophytes of the genus Pyramimonas were observed including the uncommon species P. longicauda, in addition to Micromonas pusilla and Nephroselmis pyriformis. Among the chrysophytes, the scale-bearing Paraphysomonas species (4) and the loricate Dinobryon belgica were recorded. The pedinellids (Apedinella radians and Parapedinella reticulata), the amoeba Rabdiophrys sp. and the incertae sedis (Meringosphaera mediterranea, Thaumatomastix sp.) are all scale-bearing protists. The 44 taxa (mostly scale-bearing flagellate species) identified and the finding of further undescribed Chrysochromulina species indicate that only a fraction of the species present in the region are known, and that an effort must be made to increase general knowledge of biodiversity in these southern waters.
Explicit representation for the solution to a parabolic differential identification problem in a Banach space
Authors: Anikonov Yu. E. , Lorenzi A.
Published: January 2008

We find explicit representation formulae for the solution to the identification problem (2.1) in a Banach space X, when the linear closed operator , with , generates an analytical semigroup exponentially decreasing at infinity. Such a general result is applied to a specific parabolic boundary value problem.
A New Laboratory Apparatus to Evaluate Hydrodynamic Dispersibility of Soil During Ocean Dumping
Authors: Yeung Albert T. , W. Maxwell S. , Fung Ivan W. H. , Alfred Au S. K.
Published: January 2008

Hydrodynamic dispersion of soft marine dredging during ocean dumping may cause ecologic damage of the marine environment. The dispersibility of the fine-grained marine deposit may be mitigated by soil treatment, so as to eliminate the potential ecologic damage. An apparatus is specifically designed, fabricated, and assembled to simulate the ocean dumping process, in particular the process of how the material settles through water, to evaluate the viability, feasibility, and practicality of ocean dumping of cement-treated marine deposit, and to develop a better understanding of various complex hydrodynamic and dispersion processes during ocean dumping of soft marine deposit. The design criteria and details of each component of the new apparatus are presented. The distinct advantages of the newly developed apparatus are discussed. Typical experimental results obtained by the apparatus are presented to demonstrate its simplicity of operation and versatility in the measurement of various parameters at temporal intervals.
Surgical treatment of obesity
Authors: Bult Mariëlle J F , van Dalen Thijs , Muller Alex F
Published: January 2008

More than half of the European population are overweight (body mass index (BMI) >25 and <30 kg/m2) and up to 30% are obese (BMI≥30 kg/m2). Being overweight and obesity are becoming endemic, particularly because of increasing nourishment and a decrease in physical exercise. Insulin resistance, type 2 diabetes, dyslipidemia, hypertension, cholelithiasis, certain forms of cancer, steatosis hepatis, gastroesophageal reflux, obstructive sleep apnea, degenerative joint disease, gout, lower back pain, and polycystic ovary syndrome are all associated with overweight and obesity. The endemic extent of overweight and obesity with its associated comorbidities has led to the development of therapies aimed at weight loss. The long-term effects of diet, exercise, and medical therapy on weight are relatively poor. With respect to durable weight reduction, bariatric surgery is the most effective long-term treatment for obesity with the greatest chances for amelioration and even resolution of obesity-associated complications. Recent evidence shows that bariatric surgery for severe obesity is associated with decreased overall mortality. However, serious complications can occur and therefore a careful selection of patients is of utmost importance. Bariatric surgery should at least be considered for all patients with a BMI of more than 40 kg/m2 and for those with a BMI of more than 35 kg/m2 with concomitant obesity-related conditions after failure of conventional treatment. The importance of weight loss and results of conventional treatment will be discussed first. Currently used operative treatments for obesity and their effectiveness and complications are described. Proposed criteria for bariatric surgery are given. Also, some attention is devoted to more basic insights that bariatric surgery has provided. Finally we deal with unsolved questions and future directions for research.
Long-standing, insulin-treated type 2 diabetes patients with complications respond well to short-term resistance and interval exercise training
Authors: Praet S F E , Jonkers R A M , Schep G , Stehouwer C D A , Kuipers H , Keizer H A , van Loon L J
Published: January 2008

Objective

To determine the feasibility and the benefits of combined resistance and interval exercise training on phenotype characteristics and skeletal muscle function in deconditioned, type 2 diabetes (T2D) patients with polyneuropathy.

Design

Short-term, single-arm intervention trial.

Methods

Eleven male T2D patients (age: 59.1±7.5 years; body mass index: 32.2±4.0 kg/m2) performed progressive resistance and interval exercise training thrice a week for 10 weeks. Besides primary diabetes outcome measures, muscle strength (MUST), maximal workload capacity (Wmax), whole-body peak oxygen uptake (VO2peak) and muscle oxidative capacity (MUOX), intramyocellular lipid (IMCL) and glycogen (IMCG) storage, and systemic inflammation markers were determined before and after training. Daily exogenous insulin requirements (EIR) and historic individualized EIR were gathered and analysed.

Results

MUST and Wmax increased with 17% (90% confidence intervals 9–24%) and 14% (6–21) respectively. Furthermore, mean arterial blood pressure declined with 5.5 mmHg (−9.7 to −1.4). EIR dropped with 5.0 IU/d (−11.5 to 1.5) compared with baseline. A decline of respectively −0.7 mmol/l (−2.9 to 1.5) and −147 μmol/l (−296 to 2) in fasting plasma glucose and non-esterified fatty acids concentrations were observed following the intervention, but these were not accompanied by changes in VO2peak, MUOX, IMCL or IMCG, and blood glycolysated haemoglobin, adiponectin, tumor necrosis factor-α and/or cholesterol concentrations.

Conclusion

Short-term resistance and interval exercise training is feasible in deconditioned T2D patients with polyneuropathy and accompanied by moderate improvements in muscle function and blood pressure. Such a specific exercise regimen may provide a better framework for future exercise intervention programmes in the treatment of deconditioned T2D patients.
Oncogenic hypophosphataemic osteomalacia: biomarker roles of fibroblast growth factor 23, 1,25-dihydroxyvitamin D3 and lymphatic vessel endothelial hyaluronan receptor 1
Authors: Hannan Fadil M , Athanasou Nicholas A , Teh James , Gibbons Christopher L M H , Shine Brian , Thakker Rajesh V
Published: January 2008

Oncogenic osteomalacia (OOM) is characterised by tumour production of fibroblast growth factor 23 (FGF23) that results in hypophosphataemia and renal phosphate wasting, reduced 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) synthesis and osteomalacia. Here, we demonstrate the roles of serum FGF23 and 1,25(OH)2D3, together with the lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), as biomarkers for OOM. A previously well 52-year-old man presented with a 2-year history of generalised musculoskeletal pain and proximal myopathy. He had hypophosphataemia, elevated serum alkaline phosphatase activity, low serum 1,25(OH)2D3 and a reduced tubular maximum of phosphate/glomerular filtration rate. These findings indicated a diagnosis of OOM, but magnetic resonance imaging (MRI) and octreotide scintigraphy did not identify any tumours. Treatment with oral phosphate and calcitriol resolved the symptoms and biochemical abnormalities within 6 months. Four years later, he relapsed whilst on treatment with oral phosphate and calcitriol. Serum FGF23 concentration was elevated and MRI identified a 2 cm tumour within Hoffa's fat pad of the left knee. Removal of the tumour resulted in a complete resolution of symptoms and normalisation of the serum biochemical abnormalities including serum FGF23. Histology demonstrated a phosphaturic mesenchymal tumour, mixed connective tissue variant (PMTMCT), which revealed immunostaining with anti-LYVE-1 antibody and hence the presence of lymphatic vessels. Serum FGF23 and 1,25(OH)2D3 were found to be reliable biomarkers for OOM. In addition, the demonstration of lymphatics in the PMTMCT helps to distinguish this tumour from most typical benign haemangiomas.