tbuckley/cabot-search huggingface dataset:
APOE-4 Genotype and Neurophysiological Vulnerability to Alzheimer's and Cognitive Aging
Authors: Susan Bookheimer, Alison Burggren
Journal: Annual Review of Clinical Psychology (2009)

Many years before receiving a clinical diagnosis of Alzheimer's disease (AD), patients experience evidence of cognitive decline. Recent studies using a variety of brain imaging technologies have detected subtle changes in brain structure and function in normal adults with a genetic risk for AD; these brain changes have similar pathological features as AD, and some appear to be predictive of future cognitive decline. This review examines the most recent data on brain changes in genetic risk for AD and discusses the benefits and potential risks of detecting individuals at risk.
CCL5-Mediated Th2 Immune Polarization Promotes Metastasis in Luminal Breast Cancer
Authors: Qianfei Zhang, Jilong Qin, Lin Zhong, Lei Gong, Bing Zhang, Yan Zhang, Wei-Qiang Gao
Journal: Cancer Research (2015)

The tumor-promoting chemokine CCL5 has been implicated in malignant transformation of breast epithelial cells, with studies to date focusing mainly on basal-type breast cancers. In this study, we investigated the consequences of CCL5 deletion in the MMTV-PyMT transgenic mouse model of luminal breast cancer. In this model, primary tumor burden and pulmonary metastases were reduced significantly in CCL5-deficient subjects, an effect found to be associated with a deficit of Th2 (IL4⁺CD4⁺ T) cells. Mechanistic investigations revealed that CCL5 activates CCR3, a highly expressed chemokine receptor on CD4⁺ T cells, and also boosts Gfi1 expression to promote the differentiation of Th2 cells, which enhance the prometastatic activity of tumor-associated myeloid cells. Clinically, polarization toward this immunosuppressive Th2 phenotype was also evident in patients with advanced luminal breast cancer. Thus, our findings showed that CCL5/CCR3 signaling promotes metastasis by inducing Th2 polarization of CD4⁺ T cells, with implications for prognosis and immunotherapy of luminal breast cancer.
Major histocompatibility complex independent T cell receptor-antigen interaction: functional analysis using fluorescein derivatives.
Authors: D J Diamond, P Szalay, D Symer, P Hao, H S Shin, R Z Dintzis, H M Dintzis, E L Reinherz, R F Siliciano
Journal: The Journal of Experimental Medicine (1991)

We have isolated T cell receptor (TCR) cDNAs from fluorescein (FL)-specific human T cell clones (alpha FL beta FL), and transferred them to TCR beta- Jurkat cells in order to study direct FL-binding to the TCR. Using either FL-conjugated polymers (FL-polymer) or FL-substituted Sepharose beads, we are able to demonstrate the direct binding of antigen to the T cell surface, and the functional activation of the T cell transfectants. We present evidence against the involvement of major histocompatibility complex (MHC) molecules or antigen presentation in the interaction of FL with the alpha FL beta FL transfectants. Additionally, we have examined the effect of ring substitutions on the FL molecule as well as specific alterations of substituents attached to the 5' position, and we have found that all of them interfere with the functional recognition of the alpha FL beta FL TCR. These experiments demonstrate that TCRs like antibodies have intrinsic affinities for antigen, even without the involvement of MHC molecules.
Hydrotropic magnetic micelles for combined magnetic resonance imaging and cancer therapy
Authors: Hong Yeol Yoon, Gurusamy Saravanakumar, Roun Heo, Seung Hong Choi, In Chan Song, Moon Hee Han, Kwangmeyung Kim, Jae Hyung Park, Kuiwon Choi, Ick Chan Kwon, Kinam Park
Journal: Journal of Controlled Release (2012)
Prognostic value of Doppler echocardiographic mitral inflow patterns: implications for risk stratification in patients with chronic congestive heart failure
Authors: Alexander Hansen, Markus Haass, Christian Zugck, Carsten Krueger, Kristina Unnebrink, Rainer Zimmermann, Wolfgang Kuebler, Helmut Kuecherer
Journal: Journal of the American College of Cardiology (2001)
Discussions About Clinical Trials Among Patients With Newly Diagnosed Lung and Colorectal Cancer
Authors: Kenneth L. Kehl, Neeraj K. Arora, Deborah Schrag, John Z. Ayanian, Steven B. Clauser, Carrie N. Klabunde, Katherine L. Kahn, Robert H. Fletcher, Nancy L. Keating
Journal: JNCI Journal of the National Cancer Institute (2014)

BackgroundClinical trials are essential to establish the effectiveness of new cancer therapies, but less than 5% of adults with cancer enroll in trials. In addition to ineligibility or lack of available trials, barriers to enrollment may include limited patient awareness about the option of participation.
Gamma band suppression by pseudowords: Evidence for lexical cell assemblies?
Authors: Thomas P. Urbach, Robert E. Davidson, Robert M. Drake
Journal: Behavioral and Brain Sciences (1999)

The EEG and MEG studies cited in the target article found reduced gamma band power following pseudowords in comparison with words. Pulverm&amp;uuml;ller interprets this power difference in terms of reverberating lexical cell assemblies. An alternative interpretation in terms of latency jitter in the gamma band following pseudowords is proposed that does not appeal to lexical cell assemblies.
Binding and Cytotoxicity of Conjugated and Recombinant Fusion Proteins Targeted to the Gonadotropin-Releasing Hormone Receptor
Authors: Lin Qi, Terry M. Nett, Matthew C. Allen, Xiaoming Sha, Gail S. Harrison, Barbara A. Frederick, E. David Crawford, L. Michael Glode
Journal: Cancer Research (2004)

Abstract Pokeweed antiviral protein (PAP) is a plant-derived, highly potent ribosome inactivating protein that causes inhibition of protein translation and rapid cell death. We and others have delivered this protein to various cell types, including cancer cells, using hormones to specifically target cells bearing the hormone receptor. Here, we compare binding and cytotoxicity of GnRH-PAP hormonotoxins prepared either by protein conjugation (GnRH-PAP conjugate) or through recombinant DNA technology (GnRH-PAP fusion). Although GnRH-PAP conjugate protein bound specifically to and caused cell death in cells bearing the gonadotropin-releasing hormone (GnRH) receptor, we could not detect binding or cytotoxicity using two different versions of the fusion protein in receptor-positive cells. We conclude that generation of an active GnRH-PAP fusion protein may not be feasible either because both ends of the GnRH molecule are required for receptor binding, but only the NH2 terminus is free in the fusion protein and/or that more potent analogues of GnRH (inclusion of which is not feasible in the fusion protein) are needed for efficient targeting. In contrast, the GnRH-PAP conjugate shows promise as a novel anticancer agent, capable of targeting cancer cells expressing the GnRH receptor such as prostate, breast, ovarian, endometrial, and pancreatic cells. It may also be useful as a therapeutic agent to eliminate pituitary gonadotrophs, eliminating the need for chronic GnRH analogue administration to treat hormone-sensitive diseases.
Re: Evidence for an Association Between Chlamydia psittaci and Ocular Adnexal Lymphomas
Authors: Patricia de Cremoux, Agathe Subtil, Andrés J. M. Ferreri, Anne Vincent-Salomon, Maruilio Ponzoni, Driss Chaoui, Philippe Arnaud, Livia Lumbroso-Le Rouic, Federico Sacchetti, Rémi Dendale, Martine Thioux, Marie-Christine Escande, Marc-Henri Stern, Riccardo Dolcetti, Didier Decaudin
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Ocular adnexal lymphomas may be antigendriven disorders; however, the source of the putative antigen or antigens is still unknown. Hence, we assessed whether Chlamydiae infection is associated with the development of ocular adnexal lymphomas. Methods: The presence of Chlamydia psittaci, trachomatis, and pneumoniae DNA was investigated by polymerase chain reaction in 40 ocular adnexal lymphoma samples, 20 nonneoplastic orbital biopsies, 26 reactive lymphadenopathy samples, and peripheral blood mononuclear cells (PBMCs) from 21 lymphoma patients and 38 healthy individuals. Seven patients with chlamydiapositive PBMCs were treated with the antibiotic doxycycline, and objective response was assessed in four patients with measurable lymphoma lesions. Differences in Chlamydiae DNA detection between the case patients and the control subjects were analyzed using the Fisher exact test. All statistical tests were two-sided. Results: Thirty-two of the 40 (80%) ocular adnexal lymphoma samples carried C. psittaci DNA, whereas all lymphoma samples were negative for C. trachomatis and C. pneumoniae. In contrast, none of the 20 nonneoplastic orbital biopsies (0% versus 80%; P<.001) and only three of 26 (12%) reactive lymphadenopathy samples (12% versus 80%; P<.001) carried the C. psittaci DNA. Nine of 21 (43%) patients with chlamydia-positive lymphomas carried C. psittaci DNA in their PBMCs, whereas none (0%) of the healthy PBMC donors carried C. psittaci DNA in their PBMCs (43% versus 0%; P<.001). One month after doxycycline treatment, chlamydial DNA was no longer detectable in the PBMCs of all seven treated patients, and objective response was observed in two of the four evaluable patients. Conclusion: Patients with ocular adnexal lymphoma had a high prevalence of C. psittaci infection in both tumor tissue and PBMCs. Persistent C. psittaci infection may contribute to the development of these lymphomas, as was also supported by the clinical responses observed in this study with C. psittaci– eradicating antibiotic therapy. [J Natl Cancer Inst 2004;96:586 –94]
Estimated prediagnosis radiological progression: an important tool for studying the effects of early disease modifying antirheumatic drug treatment in rheumatoid arthritis
Authors: M C Wick
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To determine if intrapatient comparisons between prediagnosis and subsequent radiological progression could be used to assess effects of DMARDs in an RA inception cohort. <b>Patients and methods:</b> 149 non-randomised patients with newly diagnosed RA in four groups were analysed: patients treated with (<i>a</i>) methotrexate (n = 56); (<i>b</i>) sulfasalazine (n = 55); (<i>c</i>) auranofin (n = 19); and (<i>d</i>) controls who were poor treatment responders (n = 19). Radiographs were quantified using the Larsen erosion score. The prediagnosis radiological progression from the onset of RA symptoms to diagnosis was calculated and compared with the observed progression rate during the first year after diagnosis while receiving DMARD treatment. <b>Results:</b> Mean (SD) disease duration from onset of symptoms until diagnosis was 6.7 (4.0) months. Mean (SD) baseline Larsen score was 13.2 (9.3), giving a mean (SD) estimated prediagnosis progression rate of 23.6 (12.4) Larsen score units/year. Control and auranofin groups showed radiological progression after diagnosis similar to the progression predicted by prediagnosis progression rates. Patients receiving methotrexate or sulfasalazine showed a marked reduction (71% and 73%, respectively; p&lt;0.001) in radiographic progression compared with prediagnosis progression. <b>Conclusions:</b> Prediagnosis rates of radiological progression can be used quantitatively to obtain information on the potential efficacy of DMARDs, and indicate that methotrexate and sulfasalazine, but not auranofin, significantly retard radiographic damage in the first year after diagnosis.
CARD15/NOD2 gene variants are associated with familially occurring and complicated forms of Crohn's disease
Authors: T Helio
Journal: Gut (2003)

Variants of the caspase activating recruitment domain 15/nucleotide oligomerisation domain 2 (CARD15/NOD2) gene have been associated with susceptibility to Crohn's disease (CD).Our aim was to evaluate the allele frequencies of the CARD15 variants R702W, G908R, and 1007fs in Finnish inflammatory bowel disease (IBD) patients and to search for possible associations between CARD15 variants and occurrence of familial forms of IBD or complicated forms of CD.We investigated 198 sporadic CD patients, 46 probands with familial CD, 27 CD probands from mixed IBD families, 99 unrelated patients with ulcerative colitis (UC), and 300 control individuals for the occurrence of the CARD15 gene variants R702W, G908R, and 1007fs.In CD patients, the allele frequencies for the rare variants of these polymorphisms were 3.3%, 0.6%, and 4.8% (total 8.7%), and the corresponding frequencies in healthy controls were 1.8%, 0%, and 1.7% (total 3.5%) (8.7% v 3.5%; p<0.01). In UC patients allele frequencies were comparable with those in controls. The frequency of the 1007fs polymorphism variant allele was significantly higher among all CD patients than in controls (4.8% v 1.7%; p<0.01) but there was no significant difference in allele frequencies between the CD and UC groups. The 1007fs allele frequency was higher in familial CD than in non-familial cases with CD (10.9% v 3.5%; p<0.01). There were no significant differences in the allele frequencies of the R702W and G908R polymorphisms between CD patients, UC patients, and controls. We found that 15.5% of CD patients, 9.1% of UC patients, and 6.7% of controls carried at least one of the CARD15 variants. In CD patients carrying at least one of the three NOD2 variants, the ileum was affected more often than in non-carrier CD patients (90% v 73%; p<0.05), they had stricturing or penetrating disease more often than non-carriers (88% v 56%; p<0.01), and they had an increased need for bowel surgery.The frequency of NOD2 gene variants was lower in genetically homogenous Finns than in other populations. The 1007fs variant was associated with CD. The occurrence of CARD15 variants predicted ileal location as well as stricturing and penetrating forms of CD.
Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study
Authors: Marianne E Pavel, John D Hainsworth, Eric Baudin, Marc Peeters, Dieter Hörsch, Robert E Winkler, Judith Klimovsky, David Lebwohl, Valentine Jehl, Edward M Wolin, Kjell Öberg, Eric Van Cutsem, James C Yao
Journal: The Lancet (2011)
Personalized Medicine for Depression: Can We Match Patients With Treatments?
Authors: Gregory E. Simon, Roy H. Perlis
Journal: American Journal of Psychiatry (2010)

Response to specific depression treatments varies widely among individuals. Understanding and predicting that variation could have great benefits for people living with depression.The authors describe a conceptual model for identifying and evaluating evidence relevant to personalizing treatment for depression. They review evidence related to three specific treatment decisions: choice between antidepressant medication and psychotherapy, selection of a specific antidepressant medication, and selection of a specific psychotherapy. They then discuss potential explanations for negative findings as well as implications for research and clinical practice.Many previous studies have examined general predictors of outcome, but few have examined true moderators (predictors of differential response to alternative treatments). The limited evidence indicates that some specific clinical characteristics may inform the choice between antidepressant medication and psychotherapy and the choice of specific antidepressant medication. Research to date does not identify any biologic or genetic predictors of sufficient clinical utility to inform the choice between medication and psychotherapy, the selection of specific medication, or the selection of a specific psychotherapy.While individuals vary widely in response to specific depression treatments, the variability remains largely unpredictable. Future research should focus on identifying true moderator effects and should consider how response to treatments varies across episodes. At this time, our inability to match patients with treatments implies that systematic follow-up assessment and adjustment of treatment are more important than initial treatment selection.
Assessment of Human Papillomavirus in Lung Tumor Tissue
Authors: Jill Koshiol, Melissa Rotunno, Maura L. Gillison, Leen-Jan Van Doorn, Anil K. Chaturvedi, Letizia Tarantini, Hebin Song, Wim G. V. Quint, Linda Struijk, Alisa M. Goldstein, Allan Hildesheim, Philip R. Taylor, Sholom Wacholder, Pietro Alberto Bertazzi, Maria Teresa Landi, Neil E. Caporaso
Journal: JNCI Journal of the National Cancer Institute (2011)

Lung cancer kills more than 1 million people worldwide each year. Whereas several human papillomavirus (HPV)–associated cancers have been identified, the role of HPV in lung carcinogenesis remains controversial. We selected 450 lung cancer patients from an Italian population–based case–control study, the Environment and Genetics in Lung Cancer Etiology. These patients were selected from those with an adequate number of unstained tissue sections and included all those who had never smoked and a random sample of the remaining patients. We used real-time polymerase chain reaction (PCR) to test specimens from these patients for HPV DNA, specifically for E6 gene sequences from HPV16 and E7 gene sequences from HPV18. We also tested a subset of 92 specimens from all never-smokers and a random selection of smokers for additional HPV types by a PCR-based test for at least 54 mucosal HPV genotypes. DNA was extracted from ethanol- or formalin-fixed paraffin-embedded tumor tissue under strict PCR clean conditions. The prevalence of HPV in tumor tissue was investigated. Specimens from 399 of 450 patients had adequate DNA for analysis. Most patients were current (220 patients or 48.9%) smokers, and 92 patients ( 20.4%) were women. When HPV16 and HPV18 type–specific primers were used, two specimens were positive for HPV16 at low copy number but were negative on additional type-specific HPV16 testing. Neither these specimens nor the others examined for a broad range of HPV types were positive for any HPV type. When DNA contamination was avoided and state-of-the-art highly sensitive HPV DNA detection assays were used, we found no evidence that HPV was associated with lung cancer in a representative Western population. Our results provide the strongest evidence to date to rule out a role for HPV in lung carcinogenesis in Western populations.
Screening Colonoscopy and Risk for Incident Late-Stage Colorectal Cancer Diagnosis in Average-Risk Adults
Authors: Chyke A. Doubeni, Sheila Weinmann, Kenneth Adams, Aruna Kamineni, Diana S.M. Buist, Arlene S. Ash, Carolyn M. Rutter, V. Paul Doria-Rose, Douglas A. Corley, Robert T. Greenlee, Jessica Chubak, Andrew Williams, Aimee R. Kroll-Desrosiers, Eric Johnson, Joseph Webster, Kathryn Richert-Boe, Theodore R. Levin, Robert H. Fletcher, Noel S. Weiss
Journal: Annals of Internal Medicine (2013)

Chinese translation Background: The effectiveness of screening colonoscopy in average-risk adults is uncertain, particularly for right colon cancer. Objective: To examine the association between screening colonoscopy and risk for incident late-stage colorectal cancer (CRC). Design: Nested case–control study. Setting: Four U.S. health plans. Patients: 1039 average-risk adults enrolled for at least 5 years in one of the health plans. Case patients were aged 55 to 85 years on their diagnosis date (reference date) of stage IIB or higher (late-stage) CRC during 2006 to 2008. One or 2 control patients were selected for each case patient, matched on birth year, sex, health plan, and prior enrollment duration. Measurements: Receipt of CRC screening 3 months to 10 years before the reference date, ascertained through medical record audits. Case patients and control patients were compared on receipt of screening colonoscopy or sigmoidoscopy by using conditional logistic regression that accounted for health history, socioeconomic status, and other screening exposures. Results: In analyses restricted to 471 eligible case patients and their 509 matched control patients, 13 case patients (2.8%) and 46 control patients (9.0%) had undergone screening colonoscopy, which corresponded to an adjusted odds ratio (AOR) of 0.29 (95% CI, 0.15 to 0.58) for any late-stage CRC, 0.36 (CI, 0.16 to 0.80) for right colon cancer, and 0.26 (CI, 0.06 to 1.11; P = 0.069) for left colon/rectum cancer. Ninety-two case patients (19.5%) and 173 control patients (34.0%) had screening sigmoidoscopy, corresponding to an AOR of 0.50 (CI, 0.36 to 0.70) overall, 0.79 (CI, 0.51 to 1.23) for right colon late-stage cancer, and 0.26 (CI, 0.14 to 0.48) for left colon cancer. Limitation: The small number of screening colonoscopies affected the precision of the estimates. Conclusion: Screening with colonoscopy in average-risk persons was associated with reduced risk for diagnosis of incident late-stage CRC, including right-sided colon cancer. For sigmoidoscopy, this association was seen for left CRC, but the association for right colon late-stage cancer was not statistically significant. Primary Funding Source: National Cancer Institute of the National Institutes of Health.
Prevalence, Predictors, and Prognostic Value of Renal Dysfunction in Adults With Congenital Heart Disease
Authors: Konstantinos Dimopoulos, Gerhard-Paul Diller, Evdokia Koltsida, Antonia Pijuan-Domenech, Sofia A. Papadopoulou, Sonya V. Babu-Narayan, Tushar V. Salukhe, Massimo F. Piepoli, Philip A. Poole-Wilson, Nicky Best, Darrel P. Francis, Michael A. Gatzoulis
Journal: Circulation (2008)

Renal insufficiency in patients with ischemic heart disease and acquired heart failure is associated with higher mortality and morbidity. We studied the prevalence of renal dysfunction in adult patients with congenital heart disease (ACHD) and its relation to outcome.A total of 1102 adult patients with congenital heart disease (age 36.0+/-14.2 years) attending our institution between 1999 and 2006 had creatinine concentration measured. Glomerular filtration rate (GFR) was calculated with the Modification of Diet in Renal Disease equation. Patients were divided into groups of normal GFR (> or =90 mL . min(-1) . 1.73 m(-2)), mildly impaired GFR (60 to 89 mL . min(-1) . 1.73 m(-2)), and moderately/severely impaired GFR (<60 mL . min(-1) . 1.73 m(-2)). Survival was compared between GFR groups by Cox regression. Median follow-up was 4.1 years, during which 103 patients died. Renal dysfunction was mild in 41% of patients and moderate or severe in 9%. A decrease in GFR was more common among patients with Eisenmenger physiology, of whom 72% had reduced GFR (<90 mL . min(-1) . 1.73 m(-2), P<0.0001 compared with the remainder), and in 18%, this was moderate or severe (P=0.007). Renal dysfunction had a substantial impact on mortality (propensity score-weighted hazard ratio 3.25, 95% CI 1.54 to 6.86, P=0.002 for moderately or severely impaired versus normal GFR).Deranged physiology in adult patients with congenital heart disease is not limited to the heart but also affects the kidney. Mortality is 3-fold higher than normal in the 1 in 11 patients who have moderate or severe GFR reduction.