tbuckley/cabot-search huggingface dataset:
The Promotion of V Region Hypermutation
Authors: Matthew D. Scharff, Vladimir Poltoratsky, Nancy S. Green
Journal: The Journal of Experimental Medicine (1997)

Higher organisms have evolved unusual molecular and genetic mechanisms to generate high affinity and highly specific antibodies to a seemingly infinite number of foreign antigens (([1][1])). Even though a highly diverse germline encoded antibody repertoire is created, most of the antibodies have low
Residual Risk of Breast Cancer Recurrence 5 Years After Adjuvant Therapy
Authors: Abenaa M. Brewster, Gabriel N. Hortobagyi, Kristine R. Broglio, Shu-Wan Kau, Cesar A. Santa-Maria, Banu Arun, Aman U. Buzdar, Daniel J. Booser, Vincente Valero, Melissa Bondy, Francisco J. Esteva
Journal: JNCI Journal of the National Cancer Institute (2008)

There is limited prognostic information to identify breast cancer patients who are at risk for late recurrences after adjuvant or neoadjuvant systemic therapy (AST). We evaluated the residual risk of recurrence and prognostic factors of 2838 patients with stage I–III breast cancer who were treated with AST between January 1, 1985, and November 1, 2001, and remained disease free for 5 years. Residual recurrence-free survival was estimated from the landmark of 5 years after AST to date of first recurrence or last follow-up using the Kaplan–Meier method. The log-rank test (two-sided) was used to compare groups. Residual recurrence-free survival rates at 5 and 10 years were 89% and 80%, respectively, and 216 patients developed a recurrence event. The 5-year residual risks of recurrence for patients with stage I, II, and III cancers were 7% (95% confidence interval [CI] = 3% to 15%), 11% (95% CI = 9% to 13%), and 13% (95% CI = 10% to 17%), respectively (P = .02). In multivariable analysis, stage, grade, hormone receptor status, and endocrine therapy were associated with late recurrences. Breast cancer patients have a substantial residual risk of recurrence, and selected tumor characteristics are associated with late recurrences.
Passive respiratory mechanics in healthy infants. Effects of growth, gender, and smoking.
Authors: J P Hanrahan, R W Brown, V J Carey, R G Castile, F E Speizer, I B Tager
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

This investigation characterizes the normal growth, variability, and effects of gender and smoking on passive respiratory mechanics in healthy infants. Passive respiratory mechanics were assessed at 193 test sessions on 127 infants (55 boys, 72 girls) between 2 wk and 18 mo of age using the single-occlusion passive flow-volume technique. Respiratory compliance (Crs) increased significantly with increasing infant length, whereas respiratory resistance (Rrs) declined. No significant gender differences were apparent for Crs, although there was a tendency for this measure to be both lower at birth and increase at a slower rate in girls than in boys. Rrs was significantly higher at birth in infant boys than in infant girls, but the rate of the normal decline in Rrs during the first 18 mo also occurred at a significantly greater rate in boys. The passive respiratory time constant (Trs) overall showed little change over this age range, but it was both lower near birth and increased at a significantly greater rate versus infant length in girls than in boys. Maternal smoking during pregnancy was associated with lower levels of Rrs at birth, as well as with significantly slower growth of Crs and natural decline of Rrs in the first 18 mo of life. These data suggest that infant girls may have more mature respiratory mechanics at birth, but that postnatal growth/maturation may be faster in boys.
Consciousness is more than wakefulness
Authors: Alain Morin
Journal: Behavioral and Brain Sciences (2007)

Merker's definition of consciousness excludes self-reflective thought, making his proposal for decorticate consciousness not particularly ground-breaking. He suggests that brainstem sites are neglected in current theories of consciousness. This is so because broader definitions of consciousness are used. Split-brain data show that the cortex is important for full-blown consciousness; also, behaviors exhibited by hydranencephaly patients and decorticated rats do not seem to require reflective consciousness.
Subclinical Rejection Phenotypes at 1 Year Post-Transplant and Outcome of Kidney Allografts
Authors: Alexandre Loupy, Dewi Vernerey, Claire Tinel, Olivier Aubert, Jean-Paul Duong van Huyen, Marion Rabant, Jérôme Verine, Dominique Nochy, Jean-Philippe Empana, Frank Martinez, Denis Glotz, Xavier Jouven, Christophe Legendre, Carmen Lefaucheur
Journal: Journal of the American Society of Nephrology (2015)

Kidney allograft rejection can occur in clinically stable patients, but long-term significance is unknown. We determined whether early recognition of subclinical rejection has long-term consequences for kidney allograft survival in an observational prospective cohort study of 1307 consecutive nonselected patients who underwent ABO-compatible, complement-dependent cytotoxicity-negative crossmatch kidney transplantation in Paris (2000-2010). Participants underwent prospective screening biopsies at 1 year post-transplant, with concurrent evaluations of graft complement deposition and circulating anti-HLA antibodies. The main analysis included 1001 patients. Three distinct groups of patients were identified at the 1-year screening: 727 (73%) patients without rejection, 132 (13%) patients with subclinical T cell-mediated rejection (TCMR), and 142 (14%) patients with subclinical antibody-mediated rejection (ABMR). Patients with subclinical ABMR had the poorest graft survival at 8 years post-transplant (56%) compared with subclinical TCMR (88%) and nonrejection (90%) groups (P<0.001). In a multivariate Cox model, subclinical ABMR at 1 year was independently associated with a 3.5-fold increase in graft loss (95% confidence interval, 2.1 to 5.7) along with eGFR and proteinuria (P<0.001). Subclinical ABMR was associated with more rapid progression to transplant glomerulopathy. Of patients with subclinical TCMR at 1 year, only those who further developed de novo donor-specific antibodies and transplant glomerulopathy showed higher risk of graft loss compared with patients without rejection. Our findings suggest that subclinical TCMR and subclinical ABMR have distinct effects on long-term graft loss. Subclinical ABMR detected at the 1-year screening biopsy carries a prognostic value independent of initial donor-specific antibody status, previous immunologic events, current eGFR, and proteinuria.
Clinical and laboratory parameters in predicting chronic urticaria duration: a prospective study of 139 patients
Authors: E. Toubi, A. Kessel, N. Avshovich, E. Bamberger, E. Sabo, D. Nusem, J. Panasoff
Journal: Allergy (2004)

Despite the disabling nature of chronic urticaria (CU), little is known about the disease's duration or the efficacy of adopting aggressive therapeutic regimens such as cyclosporine A.The aim of this study was to evaluate whether parameters such as angioedema, autologous serum test, anti-thyroid antibodies, and total IgE could predict both CU duration and severity.One hundred and thirty-nine patients suffering from CU were prospectively followed over a 5-year period for disease duration, severity and the presence of angioedema. Also investigated was the association between these clinical parameters and the subsequent detection of autologous serum test, anti-thyroid antibodies, and total IgE.CU lasted over 1 year in more than 70% of cases and in 14% it still existed after 5 years. Angioedema co-existed or appeared during the course of CU in 40% of patients and was associated with disease duration. Autologous serum test and anti-thyroid antibodies were found positive in 28 and 12% of patients, respectively, compared to none of normal individuals, P = 0.001. CU duration was associated with the presence of both autologous serum test and anti-thyroid antibodies; however, autologous serum test and not anti-thyroid antibodies was found in association with CU severity.We demonstrate for the first time that CU duration is associated with clinical parameters such as severity and angioedema, and with laboratory parameters such as autologous serum test and anti-thyroid antibodies. The ability to predict CU duration may facilitate decisions regarding the possible early initiation of cyclosporine A as a means by which to reduce disease severity and duration.
REGULATION OF CATIONIC AMINO ACID TRANSPORT: The Story of the CAT-1 Transporter
Authors: Maria Hatzoglou, James Fernandez, Ibrahim Yaman, Ellen Closs
Journal: Annual Review of Nutrition (2004)

The discovery of the function of the receptor for the ecotropic retrovirus as a membrane transporter for the essential amino acids lysine and arginine was a landmark finding in the field of molecular nutrition. This finding indicated that cationic amino acid transporters (CATs) act pathologically as viral receptors. The importance of this transporter was further supported by knockout mice that were not viable after birth. CAT-1 was the first amino acid transporter to be cloned; several other CATs were later characterized biochemically and molecularly. These transporters mediate the bidirectional transport of cationic amino acids, thus supporting important metabolic functions, such as synthesis of proteins, nitric oxide (NO) synthesis, polyamine biosynthesis, and interorgan amino acid flow. This review briefly describes the advances in the regulation of cationic amino acid transport, focusing on the molecular mechanisms that regulate the CAT-1 transporter. Of particular interest to this review is the regulation of CAT-1 by nutritional stresses, such as amino acid availability. The studies that are reviewed conclude that the CAT-1 gene is essential for cell survival during stress because it allows cells to resume growth as soon as amino acids become available.
Lessons From the Adjuvant Bevacizumab Trial on Colon Cancer: What Next?
Authors: Eric Van Cutsem, Diether Lambrechts, Hans Prenen, Rakesh K. Jain, Peter Carmeliet
Journal: Journal of Clinical Oncology (2010)

Eric Van Cutsem, University Hospital Gasthuisberg/Leuven, Katholieke Universiteit Leuven, Leuven, Belgium Diether Lambrechts, Vesalius Research Center, Vlaams Instituut voor Biotechnologie; Katholieke Universiteit Leuven, Leuven, Belgium Hans Prenen, University Hospital Gasthuisberg/Leuven, Katholieke Universiteit Leuven, Leuven, Belgium Rakesh K. Jain, Massachusetts General Hospital and Harvard Medical School, Boston, MA Peter Carmeliet, Vesalius Research Center, Vlaams Instituut voor Biotechnologie; Katholieke Universiteit Leuven, Leuven, Belgium
Reference Values for Dynamic Responses to Incremental Cycle Ergometry in Males and Females Aged 20 to 80
Authors: J. ALBERTO NEDER, LUIZ E. NERY, CLOVIS PERES, BRIAN J. WHIPP
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Interpretation of incremental cardiopulmonary exercise tests (CPET) might be enhanced by considering the simultaneous rates of change of certain key variables, e.g., Δ oxygen uptake/ Δ work rate ( ΔV˙ o 2/ Δ WR), Δ heart rate/ ΔV˙ o 2 ( Δ HR/ ΔV˙ o 2), Δ ventilation/ Δ carbon dioxide production ( ΔV˙ e/ ΔV˙ co 2), and the linearized Δ tidal volume/ ΔV˙ e ( Δ Vt/ Δ lnV˙ e) relationships. However, there are no published age- and sex-dependent reference values for these relationships that were appropriately obtained in randomly selected subjects. We therefore prospectively evaluated 120 sedentary individuals (60 male, 60 female, age 20 to 80 yr) who were randomly selected from more than 8,000 subjects, and submitted to standard ramp-incremental CPET on an electronically braked cycle ergometer. We found that sex and age significantly influenced several of the dynamic relationships, in addition to anthropometric attributes (p < 0.05). A comprehensive set of linear prediction equations is provided; the limits of normality (at the 95% confidence level) differed substantially from previous recommendations based on single discrete values. These data therefore provide a frame of reference for assessing the normalcy of the response profiles of four standard indices of metabolic, cardiovascular, and ventilatory function during rapidly incremental cycle ergometry in sedentary males and females up to 80 yr of age.
Mesenchymal stromal cells in inflammatory bowel disease: conspirators within the ‘colitogenic niche’?
Authors: Silvio Danese, Sergio Rutella, Stefania Vetrano
Journal: Gut (2012)

The term ‘stem cell niche’ refers to a spatial and temporal structure harbouring haematopoietic stem cells in close contact with accessory cell types, such as mesenchymal stromal cells (MSC). MSC were initially isolated from the bone marrow (BM) and subsequently from other sources, including adipose tissue and umbilical cord blood. MSC can be defined by phenotypic and functional criteria, and possess immunomodulating and regenerative properties that render them attractive candidates for cell therapy approaches in autoimmune and inflammatory disorders.1 ,2 MSC play a vital role in regulating haematopoiesis and give origin to crucial niche elements, such as osteoblasts, adipocytes and reticular fibroblasts.3 Intriguingly, MSC can home in to tissues in need of structural repair, where they release paracrine factors and recruit additional cell types, such as endothelial cells and macrophages.

BMMSC also regulate both innate and adaptive immune responses, leading to inhibited generation of T helper 17 (Th17) cells and promoting the reprogramming of Th17 cells into suppressive FoxP3-expressing regulatory T cells (Treg).4 Clinical trials with both locally delivered and systemic autologous BMMSC have shown promising results in terms of safety and therapeutic efficacy for patients …
DCIS Test Helps Filter At-Risk Patients
Authors: J. Peres
Journal: JNCI Journal of the National Cancer Institute (2012)

a Harris Interactive survey of 1,226 women found that 70% of program par ticipants felt more in control of their appear ances after doing the program, compared with just 60% of those who didn’t do the program. Seventy-six percent of participants were more confident in how they looked, compared with 59% among nonparticipant patients. Those are good results, Massie continued, given that people’s confidence tends to drop with a cancer diagnosis: The same survey showed the 77% of women felt confident in their appearances before treatment, compared with only 55% afterward. “This is a disease that takes so many things away,” said Massie. “It’s nice to be able to give something back.”
Nuclear Factor (NF)-κB–regulated X-chromosome–linked <i>iap</i> Gene Expression Protects Endothelial Cells from Tumor Necrosis Factor α–induced Apoptosis
Authors: Christian Stehlik, Rainer de Martin, Ichiro Kumabashiri, Johannes A. Schmid, Bernd R. Binder, Joachim Lipp
Journal: The Journal of Experimental Medicine (1998)

By differential screening of tumor necrosis factor α (TNF-α) and lipopolysaccharide (LPS)- activated endothelial cells (ECs), we have identified a cDNA clone that turned out to be a member of the inhibitor of apoptosis (iap) gene family. iap genes function to protect cells from undergoing apoptotic death in response to a variety of stimuli. These iap genes, hiap1, hiap2, and xiap were found to be strongly upregulated upon treatment of ECs with the inflammatory cytokines TNF-α, interleukin 1β, and LPS, reagents that lead to activation of the nuclear transcription factor κB (NF-κB). Indeed, overexpression of IκBα, an inhibitor of NF-κB, suppresses the induced expression of iap genes and sensitizes ECs to TNF-α–induced apoptosis. Ectopic expression of one member of the human iap genes, human X-chromosome–linked iap (xiap), using recombinant adenovirus overrules the IκBα effect and protects ECs from TNF-α– induced apoptosis. We conclude that xiap represents one of the NF-κB–regulated genes that counteracts the apoptotic signals caused by TNF-α and thereby prevents ECs from undergoing apoptosis during inflammation.
Aromatase Expression Predicts Survival in Women with Early-Stage Non–Small Cell Lung Cancer
Authors: Vei Mah, David B. Seligson, Ai Li, Diana C. Márquez, Ignacio I. Wistuba, Yahya Elshimali, Michael C. Fishbein, David Chia, Richard J. Pietras, Lee Goodglick
Journal: Cancer Research (2007)

Abstract Estrogen signaling is critical in the progression of tumors that bear estrogen receptors. In most patients with breast cancer, inhibitors that block interactions of estrogen with its receptors or suppress the production of endogenous estrogens are important interventions in the clinic. Recent evidence now suggests that estrogen also contributes to the pathogenesis of non–small cell lung cancer (NSCLC). We used a human lung cancer xenograph model system to analyze the effect of aromatase or estradiol on tumor growth. We further examined the level of protein expression of aromatase in 422 patients with NSCLC using a high-density tissue microarray. Results were confirmed and validated on an independent patient cohort (n = 337). Lower levels of aromatase predicted a greater chance of survival in women 65 years and older. Within this population, the prognostic value of aromatase was greatest in earlier stage lung cancer (stage I/II). In addition, for women with no history of smoking, lower aromatase levels were a strong predictor of survival. Our findings implicate aromatase as an early-stage predictor of survival in some women with NSCLC. We predict that women whose lung cancers have higher levels of aromatase might be good candidates for targeted treatment with aromatase inhibitors. [Cancer Res 2007;67(21):10484–90]
what is culture made of?
Authors: chen yu, linda smith
Journal: Behavioral and Brain Sciences (2005)

culture is surely important in human learning. but the relation between culture and psychological mechanism needs clarification in three areas: (1) all learning takes place in real time and through real-time mechanisms; (2) social correlations are just a kind of learnable correlations; and (3) the proper frame of reference for cognitive theories is the perspective of the learner.
Increased incidence of and impaired prognosis after acute myocardial infarction among patients with seropositive rheumatoid arthritis
Authors: A. Sodergren, B. Stegmayr, V. Lundberg, M.-L. Ohman, S. Wallberg-Jonsson
Journal: Annals of the Rheumatic Diseases (2006)

To examine the incidence and outcome of acute myocardial infarction (AMI) in patients with rheumatoid arthritis compared with the general population, and to examine whether care and treatment of an AMI differs between patients and controls.The Multinational Monitoring of Trends and Determinants of Cardiovascular Disease register for northern Sweden was used to compare those incidences of AMI in a cohort of patients with rheumatoid arthritis with that in the general population. 35 patients with rheumatoid arthritis who had also experienced an AMI were identified. For each patient with rheumatoid arthritis, three controls with a history of AMI but without rheumatoid arthritis were randomly selected from the same register, and matched for age, sex and year of the AMI for evaluation of case fatality and potential differences in treatment of AMI.The standardised incidence ratio for AMI was 2.9 in patients with rheumatoid arthritis compared with the general population (p<0.05). During the first 10 years after an AMI, patients with rheumatoid arthritis had a higher overall case fatality compared with controls (hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.02 to 2.71). Survival time was decreased in the rheumatoid arthritis group compared with controls despite the same care and treatment.Both the incidence of and case fatality after an AMI were higher among patients with rheumatoid arthritis than among the general population. The results emphasise the necessity of optimising the preventive, diagnostic and caring strategies for AMI in rheumatoid arthritis.
Fertility in luteinizing hormone receptor-knockout mice after wild-type ovary transplantation demonstrates redundancy of extragonadal luteinizing hormone action
Authors: T. Pakarainen
Journal: Journal of Clinical Investigation (2005)

The luteinizing hormone receptor (LHR), mainly expressed in gonads, is essential for normal reproduction. However, numerous recent studies have also demonstrated LHR expression in multiple extragonadal reproductive and nonreproductive tissues. Although some effects of luteinizing hormone (LH) or its agonist, human chorionic gonadotropin, have been shown in extragonadal sites, their physiological significance remains open. In the present study, we have addressed the function of the extragonadal LHR using LHR-KO mice (LuRKO mice), in which the ovaries of prepubertal mice were orthotopically replaced with pieces of WT ovary using similarly transplanted WT mice as controls. Most ovarian transplants attained normal endocrine function in both groups of mice, as demonstrated by normal age at vaginal opening, estrous cycles, and sexual behavior. Both the LuRKO and WT mice repeatedly became pregnant (9/16 vs. 16/20 after first mating; difference not significant) and delivered similarly sized litters, which grew normally after birth, indicating normal lactation. In conclusion, fertility is restored in LuRKO mice by transplantation of WT ovarian tissue. This is achieved in the absence of extragonadal LHR expression, which indicates physiological redundancy for such receptor sites.
The Immunologic Character of Acquired Inhibitors of Antihemophilic Globulin (Factor VIII) and the Kinetics of Their Interaction with Factor VIII*
Authors: Sandor S. Shapiro
Journal: Journal of Clinical Investigation (1967)

Investigations were undertaken of the chemical nature and kinetics of interaction of three acquired inhibitors of Factor VIII. The inhibition was stoichiometric, one molecule of inhibitor (or one site on a molecule) being required to inactivate one molecule of Factor VIII. All three inhibitors were found to be monotypic antibodies of class IgG, Type K (gamma(2) kappa(2)). This appears to be the second syndrome due to the production of monotypic antibody, and the first instance involving IgG immunoglobulins.