tbuckley/cabot-search huggingface dataset:
Long-Term Cancer Risk of Immunosuppressive Regimens after Kidney Transplantation
Authors: Martin P. Gallagher, Patrick J. Kelly, Meg Jardine, Vlado Perkovic, Alan Cass, Jonathan C. Craig, Josette Eris, Angela C. Webster
Journal: Journal of the American Society of Nephrology (2010)

Cancer is a widely recognized complication of transplantation, and the effects of various immunosuppressive drugs on cancer risk remains controversial. This randomized trial allocated 489 recipients of first cadaveric renal transplants to one of three groups: Azathioprine and prednisolone, cyclosporine monotherapy, or cyclosporine monotherapy followed by a switch to azathioprine and prednisolone after 3 months. Here, we report cancer outcomes by non-skin cancer (including melanoma) and skin cancer (excluding melanoma) for 481 patients during a median follow-up of 20.6 years. A total of 226 patients developed at least one cancer: 95 with non-skin cancer and 171 with skin cancer. In the intention-to-treat analysis, mean times to first non-skin cancer (16.0, 15.3, and 15.7 years for groups 1 through 3, respectively) and first skin cancer (13.6, 14.3, and 15.2 years, respectively) were not different among the three groups or between any subgroup. In multivariate analyses, non-skin cancer associated with increasing age and previous smoking history, whereas skin cancer associated with increasing age, nonbrown eye color, fairer skin, and a functioning transplant. Treatment allocation did not associate with development of either form of cancer in multivariate analyses. In conclusion, these immunosuppressive regimens, widely used in recent decades, carry similar risks for carcinogenicity after kidney transplantation.
Differential regulation of xanthine and NAD(P)H oxidase by hypoxia in human umbilical vein endothelial cells. Role of nitric oxide and adenosine
Authors: H Sohn
Journal: Cardiovascular Research (2003)

Objectives: Although in tissue injury following hypoxia/reoxygenation (H/R) an increased endothelial formation of superoxide anions (O2−) plays an important role, it is still not fully understood which of the potential enzymatic sources of endothelial O2− are crucially involved. In this study, we particularly examined the activities of NAD(P)H oxidase and xanthine oxidase (XO) after 8 h of exposure to mild hypoxia. We further studied whether enzyme activities can be modified by NO and adenosine during hypoxic treatment. Methods and results: In human umbilical vein endothelial cells O2− production was measured immediately after exposure to hypoxia ('early reoxygenation') or after 2 h of reoxygenation at normoxic conditions ('late reoxygenation'). In the early reoxygenation phase the O2− production was attenuated by 28.5% while it was enhanced by 58.2% after late reoxygenation. Using specific inhibitors of NAD(P)H oxidase and XO, gp91ds-tat and oxypurinol, respectively, we show that the constitutively active NAD(P)H oxidase was blocked following hypoxia while XO was activated. The presence of NO during hypoxia had no effect on NAD(P)H oxidase activity but it significantly inhibited the activation of XO. Inhibition of XO activation was, at least in part, caused by the release of adenosine from endothelial cells which induces an increased formation of NO by its A1 and A2 receptors. Conclusion: Our results indicate that during exposure to mild hypoxia for 8 h, a change in the enzymatic source of endothelial O2− occurs: a prolonged inhibition of NAD(P)H oxidase was found while an enhanced activity of XO occurs in the reoxygenation phase. These results suggest that different strategies of antioxidant therapy should be taken into consideration in oxidative stress related to chronic hypoxia when compared to normoxic atherosclerotic tissues with an activated vascular NAD(P)H oxidase as the main source of O2−.
Role of the Sodium-Dependent Phosphate Cotransporter, Pit-1, in Vascular Smooth Muscle Cell Calcification
Authors: Xianwu Li, Hsueh-Ying Yang, Cecilia M. Giachelli
Journal: Circulation Research (2006)

Vascular calcification is associated with cardiovascular morbidity and mortality. Hyperphosphatemia is an important contributor to vascular calcification. Our previous studies demonstrated that elevated phosphate induces calcification of smooth muscle cells (SMC) in vitro. Inhibition of phosphate transport by phosphonoformic acid blocked phosphate-induced calcification, implicating sodium-dependent phosphate cotransporters in this process. In the present study, we have investigated the role of the type III sodium-dependent phosphate cotransporter, Pit-1, in SMC calcification in vitro. Human SMC stably expressing Pit-1 small interfering double-stranded RNA (SMC-iRNA) were established using a retroviral system. SMC-iRNA had decreased Pit-1 mRNA and protein levels and sodium-dependent phosphate transport activity compared with the control transduced cells (SMC-CT) (2.9 versus 9.78 nmol/mg protein per 30 minutes, respectively). Furthermore, phosphate-induced SMC calcification was significantly inhibited in SMC-iRNA compared with SMC-CT at all time points examined. Overexpression of Pit-1 restored phosphate uptake and phosphate-induced calcification in Pit-1 deficient cells. Mechanistically, although Pit-1–mediated SMC calcification was not associated with apoptosis or cell-derived vesicles, inhibition of phosphate uptake in Pit-1 knockdown cells blocked the induction of the osteogenic markers Cbfa-1 and osteopontin. Our results indicate that phosphate uptake through Pit-1 is essential for SMC calcification and phenotypic modulation in response to elevated phosphate.
Isolation and longterm culture of human intestinal microvascular endothelial cells.
Authors: G Haraldsen, J Rugtveit, D Kvale, T Scholz, W A Muller, T Hovig, P Brandtzaeg
Journal: Gut (1995)

Microvascular endothelial cells play an important part in inflammation as well as in organ specific leucocyte traffic, and may be functionally different from large vessel endothelium in this respect. This study therefore established a method for isolation and longterm culture of human intestinal microvascular endothelial cells (HIMEC). After dissociation by collagenase/dispase/DNase of mucosal and submucosal tissue obtained from normal adult jejunum, cells were plated and cultured to subconfluence in endothelial serum free medium containing 2.5% fetal calf serum, hydrocortisone, and N6, O2-dibutyryladenosine cyclic monophosphate. Primary cultures were trypsinised and endothelial cells were isolated by paramagnetic beads armed with monoclonal antibody to CD31. Optimal growth conditions for HIMEC cultures were established, allowing up to nine passages (three months in vitro). The cells contained Weibel-Palade bodies, expressed von Willebrand factor, CD31, and VE-cadherin; and bound Ulex Europaeus lectin I. A method to establish longterm cell cultures of HIMEC will facilitate further investigation of the function of intestinal endothelial cells and their participation in physiological and pathological events in the gut.
Targeting the Mevalonate Pathway Inhibits the Function of the Epidermal Growth Factor Receptor
Authors: Angela J. Mantha, Jennifer E.L. Hanson, Glenwood Goss, Alain E. Lagarde, Ian A. Lorimer, Jim Dimitroulakos
Journal: Clinical Cancer Research (2005)

The epidermal growth factor receptor (EGFR) is a key regulator of growth, differentiation, and survival of epithelial cancers. In a small subset of tumors, the presence of activating mutations within the ATP binding site confers increased susceptibility to gefitinib, a potent tyrosine kinase inhibitor of EGFR. Agents that can inhibit EGFR function through different mechanisms may enhance gefitinib activity in patients lacking these mutations. Mevalonate metabolites play significant roles in the function of the EGFR; therefore, mevalonate pathway inhibitors may potentiate EGFR-targeted therapies.In this study, we evaluated the effect of lovastatin on EGFR function and on gefitinib activity. Effects on EGFR function were analyzed by Western blot analysis using phosphospecific antibodies to EGFR, AKT, and extracellular signal-regulated kinase. Cytotoxic effects of lovastatin and/or gefitinib were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry.Lovastatin treatment inhibited EGF-induced EGFR autophosphorylation by 24 hours that was reversed by the coadministration of mevalonate. Combining lovastatin and gefitinib treatments showed enhanced inhibition of AKT activation by EGF in SCC9 cells. The combination of 10 mumol/L lovastatin and 10 mumol/L gefitinib treatments showed cooperative cytotoxicity in all 8 squamous cell carcinomas, 4 of 4 non-small cell lung carcinoma and 4 of 4 colon carcinoma cell lines tested. Isobologram and flow cytometric analyses of three representative cell lines with wild-type EGFR ATP binding sites confirmed that this combination was synergistic inducing a potent apoptotic response.Taken together, these results show that targeting the mevalonate pathway can inhibit EGFR function. They also suggest the potential utility of combining these clinically relevant therapeutic approaches.
School air quality related to dry cough, rhinitis and nasal patency in children
Authors: M. Simoni, I. Annesi-Maesano, T. Sigsgaard, D. Norback, G. Wieslander, W. Nystad, M. Canciani, P. Sestini, G. Viegi
Journal: European Respiratory Journal (2010)

Controls for indoor air quality (IAQ) in schools are not usually performed throughout Europe. The aim of this study was to assess the effects of IAQ on respiratory health of schoolchildren living in Norway, Sweden, Denmark, France and Italy. In the cross-sectional European Union-funded HESE (Health Effects of School Environment) Study, particulate matter with a 50% cut-off aerodynamic diameter of 10 µm (PM 10 ) and CO 2 levels in a day of normal activity (full classroom) were related to wheezing, dry cough at night and rhinitis in 654 children (10 yrs) and to acoustic rhinometry in 193 children. Schoolchildren exposed to PM 10 &gt;50 μg·m −3 and CO 2 &gt;1,000 ppm (standards for good IAQ) were 78% and 66%, respectively. All disorders were more prevalent in children from poorly ventilated classrooms. Schoolchildren exposed to CO 2 levels &gt;1,000 ppm showed a significantly higher risk for dry cough (OR 2.99, 95% CI 1.65–5.44) and rhinitis (OR 2.07, 95% CI 1.14–3.73). By two-level (child, classroom) hierarchical analyses, CO 2 was significantly associated with dry cough (OR 1.06, 95% CI 1.00–1.13 per 100 ppm increment) and rhinitis (OR 1.06, 95% CI 1.00–1.11). Nasal patency was significantly lower in schoolchildren exposed to PM 10 &gt;50 μg·m −3 than in those exposed to lower levels. A poor IAQ is frequent in European classrooms; it is related to respiratory disturbances and affects nasal patency.
Blood-Based Biomarkers in Alzheimer Disease: Where Are We Now and Where Have We to Go?—Reply
Authors: Simon M. Laws, James D. Doecke, Ralph N. Martins
Journal: JAMA Neurology (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
THE MODE OF TRANSMISSION OF LEPROSY
Authors: T. L. Sandes
Journal: BMJ (1911)

THE mode of transmission of leprosy from the infected to the healthy is a question which' has hitherto baffled research.Of the infectivity of the disease no one who has studied its history and has carefully investigated any considerable nuxnber of cases, their previous life and social relations, and who considers the evidence without prejuclice, can, I think, have any doubt.In the first piace, a word as to heredity.It is ex- ceedingly improbable thjat an ovum, still less a sperm cell, could contain so relatively large an intruder as'a lepra'
Randomized, Controlled Trial of Written Emotional Expression and Benefit Finding in Breast Cancer Patients
Authors: Annette L. Stanton, Sharon Danoff-Burg, Lisa A. Sworowski, Charlotte A. Collins, Ann D. Branstetter, Alicia Rodriguez-Hanley, Sarah B. Kirk, Jennifer L. Austenfeld
Journal: Journal of Clinical Oncology (2002)

Expressing emotions and finding benefits regarding stressful experiences have been associated in correlational research with positive adjustment. A randomized trial was performed to compare effects of experimentally induced written emotional disclosure and benefit finding with a control condition on physical and psychological adjustment to breast cancer and to test whether outcomes varied as a function of participants' cancer-related avoidance.Early-stage breast cancer patients completing medical treatment were assigned randomly to write over four sessions about (1) their deepest thoughts and feelings regarding breast cancer (EMO group; n = 21), (2) positive thoughts and feelings regarding their experience with breast cancer (POS group; n = 21), or (3) facts of their breast cancer experience (CTL group; n = 18). Psychological (eg, distress) and physical (perceived somatic symptoms and medical appointments for cancer-related morbidities) outcomes were assessed at 1- and 3-month follow-ups.A significant condition x cancer-related avoidance interaction emerged on psychological outcomes; EMO writing was relatively effective for women low in avoidance, and induced POS writing was more useful for women high in avoidance. Significant effects of experimental condition emerged on self-reported somatic symptoms (P =.0183) and medical appointments for cancer-related morbidities (P =.0069). Compared with CTL participants at 3 months, the EMO group reported significantly decreased physical symptoms, and EMO and POS participants had significantly fewer medical appointments for cancer-related morbidities.Experimentally induced emotional expression and benefit finding regarding early-stage breast cancer reduced medical visits for cancer-related morbidities. Effects on psychological outcomes varied as a function of cancer-related avoidance.
Late presentation of dyskeratosis congenita as apparently acquired aplastic anaemia due to mutations in telomerase RNA
Authors: Patrick F Fogarty, Hiroki Yamaguchi, Adrian Wiestner, Gabriela M Baerlocher, Elaine Sloand, Weihua S Zeng, Elizabeth J Read, Peter M Lansdorp, Neal S Young
Journal: The Lancet (2003)
Minor Myocardial Damage and Prognosis
Authors: K. Martijn Akkerhuis, John H. Alexander, Barbara E. Tardiff, Eric Boersma, Robert A. Harrington, A. Michael Lincoff, Maarten L. Simoons
Journal: Circulation (2002)

The relevance of the adverse prognostic implications of CK-MB elevation after percutaneous coronary intervention (PCI) remains controversial. Therefore, we compared the relationship between the level of postprocedural CK-MB elevation and 6-month mortality in patients undergoing PCI with the relationship between the level of spontaneous, non-PCI-related CK-MB elevation and 6-month mortality in patients with acute coronary syndromes (ACS) treated medically.In the PURSUIT trial, 5583 of 9461 patients who presented with a non-ST-elevation ACS did not undergo PCI or CABG and had at least 1 CK-MB sample collected during index-hospitalization. There was a gradual increase in 6-month mortality with higher CK-MB levels: 4.1%, 8.6%, 9.0%, 14.3%, 15.5% for CK-MB ratios 0 to 1, >1 to 3, >3 to 5, >5 to 10, and >10 times the upper limit of normal. A combined analysis in 8838 patients undergoing PCI in 5 large, clinical trials revealed a proportional relationship between postprocedural CK-MB levels (</= 48 hours after PCI) and 6-month mortality. In patients with CK-MB ratios 0 to 1, >1 to 3, >3 to 5, >5 to 10, and >10, the risk of death was 1.3%, 2.0%, 2.3%, 4.3%, and 7.4%, respectively. The absolute mortality rates were lower after procedure-related infarcts compared with spontaneous infarcts. Yet, the relative increase in 6-month mortality with each increase in peak CK-MB level was similar for PCI-related myocardial necrosis and spontaneous myocardial necrosis, as all tests for heterogeneity of the odds ratios were nonsignificant.The present analysis indicates that the adverse prognostic implications of periprocedural myocardial necrosis should be considered similar to the adverse consequences of spontaneous myocardial necrosis.
S58 TB co-infection is associated with poor survival among HIV infected patients in england and wales
Authors: D Zenner, S Conti, Z Yin, M Kall, M Kruijshaar, B Rice, M Lipman, A Pozniak, I Abubakar, V Delpech
Journal: Thorax (2013)

<h3>Introduction</h3> Tuberculosis (TB) rates in the UK are amongst the highest in Western Europe and HIV-TB co-infection (HIV-TB) contributes significantly to the burden of TB in the UK. Globally, HIV-TB is associated with significant morbidity and mortality, in particular where there is delayed diagnosis. Analysis of setting-specific survival can inform local healthcare policy. Here we report the outcome of individuals diagnosed with HIV in the UK, with particular emphasis on TB co-infection. <h3>Methodology</h3> We examined deaths among a retrospective national cohort of adults (15 years +) diagnosed with HIV infection between 2000–2008 linked to the national TB databases and death records from the Office of National Statistics to mid-2010. Hazard ratios (HR) estimates using uni- and multi-variable Cox regression modelling were calculated to compare all-cause and AIDS-specific mortality by key demographic and clinical markers. <h3>Results</h3> A total of 1,880 (4.3%) deaths were observed among 44,050 HIV-diagnosed adults during 149,663 person-years of follow-up. 3,188 (7.2%) adults developed TB and HIV-TB cases accounted for 341 (18.1%) of all deaths of whom 270 (79.2%) were late presenters (CD4&lt;200 at HIV diagnosis). One year mortality after HIV diagnosis was 45% overall and greater among HIV-TB cases (54%) and those with low CD4 counts at diagnosis (69% for CD4&lt;50). TB co-infection and a low CD4 count at HIV diagnosis significantly increased the hazard of all-cause mortality. In the fully adjusted model, the highest HR was among adults with extrapulmonary TB and pulmonary TB cases with CD4 count &lt;100 at diagnosis (figure 1). The Cox model of AIDS-specific mortality showed similar findings, albeit with increased effect size. Increasing age, female sex, UK country of birth, heterosexual route of exposure to HIV and other AIDS conditions were also associated with poor survival. Antiretroviral therapy (ART) was protective, even if interrupted. <h3>Discussion</h3> Despite the availability of effective ART and TB screening and treatment, we observed high death rates among a large national HIV cohort associated with late diagnosis and TB infection. The findings highlight the on-going need for expanded HIV testing and increased TB case finding among HIV diagnosed adults to ensure appropriate and early treatment initiation for both conditions.
Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial
Authors: Kathy S Albain, William E Barlow, Steven Shak, Gabriel N Hortobagyi, Robert B Livingston, I-Tien Yeh, Peter Ravdin, Roberto Bugarini, Frederick L Baehner, Nancy E Davidson, George W Sledge, Eric P Winer, Clifford Hudis, James N Ingle, Edith A Perez, Kathleen I Pritchard, Lois Shepherd, Julie R Gralow, Carl Yoshizawa, D Craig Allred, C Kent Osborne, Daniel F Hayes
Journal: The Lancet Oncology (2009)
Molecular Pathways: Pathogenesis and Clinical Implications of Microbiome Alteration in Esophagitis and Barrett Esophagus
Authors: Liying Yang, Fritz Francois, Zhiheng Pei
Journal: Clinical Cancer Research (2012)

Abstract Esophageal adenocarcinoma is preceded by the development of reflux-related intestinal metaplasia or Barrett esophagus, which is a response to inflammation of the esophageal squamous mucosa, reflux esophagitis. Gastroesophageal reflux impairs the mucosal barrier in the distal esophagus, allowing chronic exposure of the squamous epithelium to the diverse microbial ecosystem or microbiome and inducing chronic inflammation. The esophageal microbiome is altered in both esophagitis and Barrett esophagus, characterized by a significant decrease in gram-positive bacteria and an increase in gram-negative bacteria in esophagitis and Barrett esophagus. Lipopolysaccharides (LPS), a major structure of the outer membrane in gram-negative bacteria, can upregulate gene expression of proinflammatory cytokines via activation of the Toll-like receptor 4 and NF-κB pathway. The potential impact of LPS on reflux esophagitis may be through relaxation of the lower esophageal sphincter via inducible nitric oxide synthase and by delaying gastric emptying via cyclooxygenase-2. Chronic inflammation may play a critical role in the progression from benign to malignant esophageal disease. Therefore, analysis of the pathways leading to chronic inflammation in the esophagus may help to identify biomarkers in patients with Barrett esophagus for neoplastic progression and provide insight into molecular events suitable for therapeutic intervention in prevention of esophageal adenocarcinoma development in patients with reflux esophagitis and Barrett esophagus. Clin Cancer Res; 18(8); 2138–44. ©2012 AACR.
Tumor thickness and adnexal extension of superficial basal cell carcinoma (sBCC) as determinants of treatment failure for methylaminolevulinate (MAL)-photodynamic therapy (PDT), imiquimod, and 5-fluorouracil (FU)
Authors: Marieke H. Roozeboom, Lotte van Kleef, Aimee H.M.M. Arits, Klara Mosterd, Veronique J.L. Winnepenninckx, Arienne M.W. van Marion, Patty J. Nelemans, Nicole W.J. Kelleners-Smeets
Journal: Journal of the American Academy of Dermatology (2015)
Bone mineral density and body composition of the United States Olympic women's field hockey team
Authors: P B Sparling, T K Snow, L B Rosskopf, E M O'Donnell, P S Freedson, W C Byrnes
Journal: British Journal of Sports Medicine (1998)

To evaluate total bone mineral density (BMD) and body composition (% fat) in world class women field hockey players, members of the 1996 United States Olympic team.Whole body BMD (g/cm2) and relative body fatness (% fat) were assessed by dual energy x ray absorptiometry using a Lunar DPX-L unit with software version 1.3z. Body composition was also estimated by hydrostatic weighing and the sum of seven skinfolds.Mean (SD) BMD was 1.253 (0.048) g/cm2 which is 113.2 (4.0)% of age and weight adjusted norms. Estimates of body composition from the three methods were similar (statistically non-significant): 16.1 (4.4)% fat from dual energy x ray absorptiometry, 17.6 (3.2)% from hydrostatic weighing, and 16.9 (2.6)% from the sum of seven skinfolds. Mean fat free mass was approximately 50 kg.The mean whole body BMD value for members of the 1996 United States Olympic women's field hockey team is one of the highest reported for any women's sports team. Moreover, the mean fat free mass per unit height was quite high and % fat was low. In this group of world class sportswomen, low % fat was not associated with low BMD.