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THe STUDY ON RISK FACTORS ASSOCIATeD WITH BReAST CANceR AMONG WOMeN IN TIANJIN, CHINA AND ADeLAIDe, AUSTRALIA

Chinese Journal of Cancer Research 1989年第4期1卷 58-62页

作者：张安玉 thomas e Rohan 武光林 Department of epidemiology Tianjin Medical College Department of environmental and Preventive Medicine The Medical College of St. Bartholomew's Hospital University of London Department of epidemiology Tianjin Medical Collegeo explore the possible explanation of the marked difference in the incidence of breast cancer between Chinese and Australian women the authors have compared and analysed the results of two case-control studies completed recently in Tianjin China and Adelaide Australia. Of 10 known risk factors for breast cancer 9 were significantly higher in level in Adelaide women than in Tianjin women i.e. women in Adelaide were much taller heavier more obese earlier at menarche later at first full-term pregnancy more nulliparous less parity more in history of breast cancer in first degree relatives more educated. From the 7 risk factors analysed by use of logistic regression model 5 factors i.e. earlier age at menarche later age at first full-term pregnancy less parity history of benign disease and history of breast cancer in first degree relatives were associated significantly with the increased risk for breast cancer in the Tianjin study but not in Adelaide study. These factors being not associated with breast cancer in Adelaide women were unexpected. The explanation of the indefinite findings in Adelaide study was due to the fact that the level of the risk factor is universally high relatively uniform and lack of categories. The difference in the risk factor distribution between cases and controle would not be seen in case-control studies and significance of the risk factor therefore may not be found. According to data on diet survey in these two cities the calories from fat was significantly higher in Adelaide women than in Tianjin women. The marked difference in incidence in women in the two cities resulted from the summing-up effect of a number of factors. The important role of fat intake in geographical incidence difference and in the development of breast cancer was also

To explore the possible explanation of the marked difference in the incidence of breast cancer between Chinese and Australian women, the authors have compared and analysed the results of two case-control studies completed recently in Tianjin, China and Adelaide, Australia. Of 10 known risk factors for breast cancer 9 were significantly higher in level in Adelaide women than in Tianjin women, i.e., women in Adelaide were much taller, heavier, more obese, earlier at menarche, later at first full-term pregnancy, more nulliparous, less parity, more in history of breast cancer in first degree relatives, more educated. From the 7 risk factors analysed by use of logistic regression model 5 factors, i.e., earlier age at menarche, later age at first full-term pregnancy, less parity, history of benign disease, and history of breast cancer in first degree relatives, were associated significantly with the increased risk for breast cancer in the Tianjin study, but not in Adelaide study. These factors being not associated with breast cancer in Adelaide women were unexpected. The explanation of the indefinite findings in Adelaide study was due to the fact that the level of the risk factor is universally high, relatively uniform and lack of categories. The difference in the risk factor distribution between cases and controle would not be seen in case-control studies, and significance of the risk factor therefore may not be found. According to data on diet survey in these two cities, the calories from fat was significantly higher in Adelaide women than in Tianjin women. The marked difference in incidence in women in the two cities resulted from the summing-up effect of a number of factors. The important role of fat intake in geographical incidence difference and in the development of breast cancer was also discussed.

关键词： THe STUDY ON RISK FACTORS ASSOCIATeD WITH BReAST CANceR AMONG WOMeN IN TIANJIN AUSTRALIA CHINA AND ADeLAIDe

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A plant-based diet and animal protein： questioning dietary fat and consideringanimal protein as the main cause of heart disease

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Journal of Geriatric Cardiology 2017年第5期14卷 331-337页

作者： thomas Colin Campbell emeritus of Nutritional Biochemistry Cornell University 8 Fiddlers Green Lansing NY 14882 USA.

Dietary ＇fat＇（e.g., oils, triglycerides, cholesterol） haslong been considered a major risk factor for cardiovascularand related diseases. As reviewed elsewhere,Vogel in1847 identified cholesterol as a major compo... 详细信息

关键词： Cardiovascular disease Cholesterol Dietary protein

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effect of nutritional counselling on hepatic,muscle and adipose tissue fat content and distribution in non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2006年第36期12卷 5813-5819页

作者： e Louise thomas Audrey e Brynes Gavin Hamilton Nayna Patel Adam Spong Robert D Goldin Gary Frost Jimmy D Bell Simon D Taylor-Robinson The Robert Steiner MR Unit MRC Clinical Sciences Centre Department of Nutrition and Dietetics The Robert Steiner MR Unit MRC Clinical Sciences Centre Faculty of Medicine Imperial College London Hammersmith Hospital Du Cane Rd London W12 0HS United Kingdom and Histopathology Department Faculty of Medicine Imperial College London St Mary's Hospital Praed Street London W2 1NY United Kingdom Faculty of Medicine Faculty of Medicine Imperial College London St Mary's Hospital Praed Street London W2 1NY United Kingdom

AIM： To assess the effectiveness of the current UK clinical practice in reducing hepatic fat （IHCL）.MeTHODS： Whole body MRI and IH MRS were obtained, before and after 6 mo nutritional counselling, from liver, soleus and tibialis muscles in 10 subjects with non-alcoholic fatty liver disease （NAFLD）.ReSULTS： A 500 Kcal-restricted diet resulted in an average weight loss of 4% （-3.4 kg,） accompanied by significant reductions in most adipose tissue （AT） depots, including subcutaneous （-9.9%）, abdominal subcutaneous （-10.2%） and intra-abdominal- AT （-11.4%）. Intramyocellular lipids （IMCL） were significantly reduced in the tibialis muscle （-28.2%）. Decreases in both IHCL （-39.9%） and soleus IMCL （-12.2%） content were also observed, although these were not significant. Several individuals showed dramatic decreases in IHCL, while others paradoxically showed increases in IHCL content. Changes in body composition were accompanied by improvements in certain liver function tests： serum aspartate aminotransferase （AST） and alanine aminotransferase （ALT）. Significant correlations were found between decreases in IHCL and reductions in both intra-abdominal and abdominal subcutaneous AT. Improvements in liver function tests were associated with reductions in intra-abdominal AT, but not with changes in IHCL. CONCLUSION： This study shows that even a very modest reduction in body weight achieved through lifestyle modification can result in changes in body fat depots and improvements in LeTs.

关键词： Intra-abdominal adipose tissue Intrahepatic fat Intramyocellular lipids Weiqht loss Magnetic resonance imaging

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STAT3 mediates C6-ceramide-induced cell death in chronic lymphocytic leukemia

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Signal Transduction and Targeted Therapy 2017年第1期2卷 61-72页

作者： Ushma A Doshi Jeremy Shaw Todd e Fox David F Claxton thomas P Loughran Mark Kester Department of Pharmacology Penn State College of MedicineHersheyPAUSA Department of experimental Pathology University of Virginia School of MedicineCharlottesvilleVAUSA Department of Pharmacology University of Virginia School of MedicineCharlottesvilleVAUSA Division of Hematology and Oncology Penn State Milton S Hershey Medical Center and College of MedicineHersheyPAUSA Department of Medicine University of Virginia School of MedicineCharlottesvilleVAUSA NanoSTAR Institute University of VirginiaCharlottesvilleVAUSA

The pathogenesis of chronic lymphocytic leukemia(CLL)is poorly understood and it remains incurable with current *** have previously shown that nanoliposomal C6-ceramide(CNL)is an effective therapy in an in vivo murine model of ***,the key signaling pathways mediating CNL-induced cell death in CLL remains *** hypothesized that CNL targets STAT3,a critical regulator of hematopoietic *** observed that CNL treatment reduced phosphorylated STAT3 at both Y705 and S727 residues in CLL cell lines and patient ***,in turn,reduced STAT3 transcriptional activity and expression of critical STAT3-dependent survival factors like Mcl-1 and *** effect of CNL on STAT3 was further confirmed ex vivo as shown by reduced STAT3 phosphorylation in xenograft tumors obtained from mice treated with *** suppressed STAT3 phosphorylation at Y705 and S727 through reduction in BTK activity and MeK1/2 kinase/PKC activities,***,a synergistic reduction in CLL cell viability was observed on co-treatment with CNL and the BTK inhibitor,*** of an oncogenic form of STAT3 conferred partial resistance to CNL,providing confirmation that STAT3 mediates CNL-induced cell *** together,these findings provide the first body of evidence demonstrating ceramide regulation of STAT3 *** results are also the first to demonstrate an effect of ceramide on BTK,a critical kinase mediating the B-cell receptor signaling in CLL cells and suggest a novel and synergistic combination of CNL and BTK inhibitors for CLL treatment.

关键词： STAT3 lymphocytic media

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Boosting the superconducting spin valve effect in a metallic superconductor/ferromagnet heterostructure

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Nano Research 2016年第4期9卷 1005-1011页

作者： Pavel V. Leksin Andrey A. Kamashev Joachim Schumann Vladislav e. Kataev Jurgen thomas Bernd Buchner ilgiz A. Garifullin Leibniz Institute for Solid State and Materials Research Dresden (IFW Dresden) DoO 1171 Dresden Germany Zavoisky Physical-Technical Institute Russian Academy of Sciences 420029 Kazan Russia Dresden University of Technology D-01062 Dresden Germany

Superconducting spin valves based on the superconductor/ferromagnet （S/F） proximity effect are considered to be a key element in the emerging field of superconducting spintronics. Here, we demonstrate the crucial role of the morphology of the superconducting layer in the operation of a multilayer S/F1/F2 spin valve. We study two types of superconducting spin valve heterostructures, with rough and with smooth superconducting layers, using transmission electron microscopy in combination with transport and magnetic characterization. We find that the quality of the S/F interface is not critical for the S/F proximity effect, as regards the suppression of the critical temperature of the S layer. However, it appears to be of paramount importance in the performance of the S/F1/F2 spin valve. As the morphology of the S layer changes from the form of overlapping islands to a smooth case, the magnitude of the conventional superconducting spin valve effect significantly increases. We attribute this dramatic effect to a homogenization of the Green function of the superconducting condensate over the S/F interface in the S/F1/F2 valve with a smooth surface of the S laver.

关键词： spintronics superconductivi ferromagnetism proximity effect

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Hepatic abscess associated with Salmonella serotype B in a chronic alcoholic patient

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Hepatobiliary & Pancreatic Diseases International 2013年第4期12卷 440-442页

作者： Sidhartha S Tulachan Charles e Wilkins Anthony F Cutrona David Gemmel thomas P Marnejon Department of Internal Medicine St Elizabeth Health Center1044 Belmont AvenueYoungstown OH 44501 USA Department of Infectious Disease St Elizabeth Health Center1044 Belmont AvenueYoungstown OH 44501 USA Department of Research St Elizabeth Health Center1044 Belmont AvenueYoungstown OH 44501 USA

BACKGROUND: Hepatic abscess secondary to Salmonella is extremely rare in the United States and other Western countries. MeTHODS: A 43-year-old Caucasian man, with a history of chronic alcohol abuse, was admitted to the hospital for intermittent abdominal pain, fever and diarrhea. Clinical radiological and laboratory results were analyzed. Medical literature in PubMed pertaining to similar cases was reviewed. ReSULTS: Stool culture was positive for Salmonella serotype B and a CT scan of the abdomen with contrast was consistent with a solitary hepatic abscess. Appropriate intravenous antibiotics followed by oral maintenance therapy for six weeks resulted in a complete clinical recovery and radiographic resolution. CONCLUSIONS: The cause of Salmonella hepatic abscess in our patient was most likely associated with decreased mucosal resistance to the bacteria, seeding of infection via transient portal bacteremia and loss of host immunity. Our case highlights the fact that appropriate antibiotic alone is sufficient in the management of a solitary hepatic abscess less than 3-5 cm.

关键词： hepatic abscess Salmonella alcoholic hypochlorhydria antibiotics

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Daily activity rhythms, chronotypes, and risk-taking behavior in the signal crayfish

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Current Zoology 2022年第2期68卷 177-183页

作者： Valerio SBRAGAGLIA thomas BReITHAUPT Department of Marine Renewable Resources Marine Science Institute(ICM-CSIC)Passeig Maritim de la Barceloneta3708003 BarcelonaSpain Department of Biology and ecology of Fishes Leibniz-lnstitute of Freshwater Ecology and Inland FisheriesMüggelseedamm 31012587 BerlinGermany Department of Biological and Marine Sciences University of HullCottingham RoadHull HU67RXUK

Consistent inter-individual differences in daily activity rhythms(i.e.,chronotypes)can have ecological consequences in determining access to food resources and avoidance of *** most common measure to characterize chronotypes in animals as well as humans is the onset of activity(i.e.,early or late chronotypes).However,daily activity rhythms may also differ in the relative amount of activity displayed at particular time ***,chronotypes may also be linked to other consistent inter-individual differences in behavior(i.e.,personality),such as the propensity to take ***,we used the signal crayfish Pacifastacus leniusculusto test the presence of chronotypes and risk-taking personality traits and a potential behavioral syndrome between these *** first exposed crayfish to 5 days of light-darkness to measure daily activity rhythms and then we applied a visual predator-simulating stimulus in 2 different contexts(neutral and food).Our results showed consistent(i.e.,across 5 days)inter-individual differences in the relative nocturnal activity displayed in the early and middle,but not in the late part of darkness ***,while crayfish displayed inter-individual differences in risk-taking behavior,these were not found to be consistent across 2 ***,we were not able to formally test a behavioral syndrome between these 2 *** conclusion,our study provides the first evidence of chronotypes in the relative amount of activity displayed at particular time *** could be a valuable information for applied ecological aspects related to the signal crayfish,which is a major invasive species of freshwater ecosystems.

关键词： behavioral syndrome biological rhythms boldness feeding locomotor activity

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Promises and pitfalls of targeted agents in chronic lymphocytic leukemia

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Cancer Drug Resistance 2020年第3期3卷 415-444页

作者： thomas e.Lew Mary Ann Anderson John F.Seymour Department of Clinical Haematology The Royal Melbourne Hospital and Peter MacCallum Cancer CentreParkville 3050Australia. Blood cells and Blood Cancer Division Walter and Eliza Hall Institute of Medical ResearchParkville 3050Australia. Faculty of Medicine Dentistry and Health SciencesThe University of MelbourneParkville 3050Australia.

Targeted agents have significantly improved outcomes for patients with chronic lymphocytic leukemia,particularly high-risk subgroups for whom chemoimmunotherapy previously offered limited *** classes of agent in particular,the Bruton tyrosine kinase inhibitors(e.g.,ibrutinib)and the B-cell lymphoma 2 inhibitor,venetoclax,induce high response rates and durable remissions in the relapsed/refractory and frontline ***,maturing clinical data have revealed promises and pitfalls for both *** drugs induce remissions and disease control in the majority of patients,often in situations where modest efficacy would be expected with traditional chemoimmunotherapy ***,in the relapsed and refractory setting,both agents appear to be associated with an inevitable risk of disease relapse and *** patterns of resistance are being described for both agents but a common theme appears to be multiple sub-clonal drivers of disease *** these mechanisms and developing effective and safe methods to circumvent the emergence of resistance will determine the longer-term utility of these agents to improve patients’quality and length of *** drug combinations,optimised scheduling and sequencing of therapy will likely hold the key to achieving these important goals.

关键词： Chronic lymphocytic leukemia drug resistance venetoclax B-cell lymphoma 2 ibrutinib bruton tyrosine kinase idelalisib phosphatidylinositol 3-kinase

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The hypoxia-inducible factor-1α activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia

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Bone Research 2016年第2期4卷 85-90页

作者： Qian Zhang Michele Doucet Ryan e Tomlinson Xiaobin Han L Darryl Quarles Michael T Collins thomas L Clemens Department of Orthopaedic Surgery Johns Hopkins University Baltimore MD USA Department of Medicine University of Tennessee Health Science Center Memphis TN USA Skeletal Clinical Studies Unit craniofacial and Skeletal Diseases Branch National Institutes of HealthBethesda MD USA Baltimore Veterans Administration Medical center Baltimore MD USA

Tumor-induced osteomalacia （TIO） is a rare paraneoplastic syndrome in which ectopic production of fibroblast growth factor 23 （FGF23） by non-malignant mesenchymal tumors causes phosphate wasting and bone fractures. Recent studies have implicated the hypoxia-inducible factor-la （HIF-la） in other phosphate wasting disorders caused by elevated FGF23, including X-linked hypophosphatemic rickets and autosomal dominant hypophosphatemia. Here we provide evidence that HIF-la mediates aberrant FGF23 in TIO by transcriptionally activating its promoter. Immunohistochemical studies in phosphaturic mesenchymal tumors resected from patients with documented TIO showed that HIF-la and FGF23 were co-localized in spindle- shaped cells adjacent to blood vessels. Cultured tumor tissue produced high levels of intact FGF23 and demonstrated increased expression of HIF-la protein. Transfection of MC3T3-e1 and Saos-2 cells with a HIF-la expression construct induced the activity of a FGF23 reporter construct. Prior treatment of tumor organ cultures with HIF-la inhibitors decreased HIF-la and FGF23 protein accumulation and inhibited HIF-la-induced luciferase reporter activity in transfected cells. Chromatin immunoprecipitation assays confirmed binding to a HIF-la consensus sequence within the proximal FGF23 promoter, which was eliminated by treatment with a HIF-la inhibitor. These results show for the first time that HIF-la is a direct transcriptional activator of FGF23 and suggest that upregulation of HIF-la activity in TIO contributes to the aberrant FGF23 production in these patients.

关键词： The hypoxia-inducible factor-1 activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia HIF

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CD28 ligation increases macrophage suppression of T-cell proliferation

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cellular & Molecular Immunology 2012年第4期9卷 341-349页

作者： Daniel Silberman Amanda Bucknum thomas Bartlett Gabriella Composto Megan Kozlowskil Amanda Walker Amy Werda Jackelyn Cua Arlene H Sharpe John e Somerville James e Riggs Department of Biology Rider University Lawrenceville NJ 08648 USA Department of Pathology Harvard Medical School Cambridge MA 02115 USA Immunosciences Bristol-Myers Squibb Princeton NJ 08543 USA

When compared to spleen or lymph node cells, resident peritoneal cavity cells respond poorly to T-cell activation in vitro. The greater proportional representation of macrophages in this cell source has been shown to actively suppress the T-cell response. Peritoneal macrophages exhibit an immature phenotype （MHC class Iilo, B7lo） that reduces their efficacy as antigen-presenting cells. Furthermore, these cells readily express inducible nitric oxide synthase （iNOS）, an enzyme that promotes T-cell tolerance by catabolism of the limiting amino acid arginine. Here, we investigate the ability of exogenous T-cell costimulation to recover the peritoneal T-cell response. We show that CD28 ligation failed to recover the peritoneal T-cell response and actually suppressed responses that had been recovered by inhibiting iNOS. As indicated by cytokine eLISpot and neutralizing monoclonal antibody （mAb） treatment, this ＇cosuppression＇ response was due to CD28 ligation increasing the number of interferon （IFN）-y-secreting cells. Our results illustrate that cellular composition and cytokine milieu influence T-cell costimulation biology.

关键词： CD28 costimulation macrophages suppression

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