tbuckley/cabot-search huggingface dataset:
Effect of Occult Metastases on Survival in Node-Negative Breast Cancer
Authors: Donald L. Weaver, Takamaru Ashikaga, David N. Krag, Joan M. Skelly, Stewart J. Anderson, Seth P. Harlow, Thomas B. Julian, Eleftherios P. Mamounas, Norman Wolmark
Journal: New England Journal of Medicine (2011)

Retrospective and observational analyses suggest that occult lymph-node metastases are an important prognostic factor for disease recurrence or survival among patients with breast cancer. Prospective data on clinical outcomes from randomized trials according to sentinel-node involvement have been lacking.We randomly assigned women with breast cancer to sentinel-lymph-node biopsy plus axillary dissection or sentinel-lymph-node biopsy alone. Paraffin-embedded tissue blocks of sentinel lymph nodes obtained from patients with pathologically negative sentinel lymph nodes were centrally evaluated for occult metastases deeper in the blocks. Both routine staining and immunohistochemical staining for cytokeratin were used at two widely spaced additional tissue levels. Treating physicians were unaware of the findings, which were not used for clinical treatment decisions. The initial evaluation at participating sites was designed to detect all macrometastases larger than 2 mm in the greatest dimension.Occult metastases were detected in 15.9% (95% confidence interval [CI], 14.7 to 17.1) of 3887 patients. Log-rank tests indicated a significant difference between patients in whom occult metastases were detected and those in whom no occult metastases were detected with respect to overall survival (P=0.03), disease-free survival (P=0.02), and distant-disease-free interval (P=0.04). The corresponding adjusted hazard ratios for death, any outcome event, and distant disease were 1.40 (95% CI, 1.05 to 1.86), 1.31 (95% CI, 1.07 to 1.60), and 1.30 (95% CI, 1.02 to 1.66), respectively. Five-year Kaplan-Meier estimates of overall survival among patients in whom occult metastases were detected and those without detectable metastases were 94.6% and 95.8%, respectively.Occult metastases were an independent prognostic variable in patients with sentinel nodes that were negative on initial examination; however, the magnitude of the difference in outcome at 5 years was small (1.2 percentage points). These data do not indicate a clinical benefit of additional evaluation, including immunohistochemical analysis, of initially negative sentinel nodes in patients with breast cancer. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003830.).
The Epigenome as a Target for Cancer Chemoprevention
Authors: L. Kopelovich
Journal: JNCI Journal of the National Cancer Institute (2003)

Epigenetic events, a key driving force in the development of cancer, are alterations in gene expression without changes in the DNA coding sequence that are heritable through cell division. Such changes occur throughout all stages of tumorigenesis, including the early phases, and are increasingly recognized as major mechanisms involved in silencing tumor suppressor genes. Epigenetic changes can be reversed by the use of small molecules and, thus, such changes are promising targets for cancer chemopreventive drug development. This review examines the basis for targeting the epigenome as a prevention strategy, focusing on understanding the epigenetic changes that occur before the development of frank malignancy, when chemopreventive intervention will have the maximal impact.
Proteins involved in DNA damage response pathways and survival of stage I non-small-cell lung cancer patients
Authors: C M Choi, S C Yang, H J Jo, S Y Song, Y J Jeon, T W Jang, D J Kim, S H Jang, S H Yang, Y D Kim, K H Lee, S J Jang, Y T Kim, D K Kim, D H Chung, L Kim, H S Nam, J H Cho, H J Kim, J S Ryu
Journal: Annals of Oncology (2012)
THE EFFECT OF TESTICLE EXTRACT ON THE GROWTH OF TRANSPLANTABLE MOUSE TUMORS
Authors: Radford C. Tanzer
Journal: The Journal of Experimental Medicine (1932)

Grafts of a transplantable mouse sarcoma designated as No. 180, and those of an attenuated strain of a more malignant Sarcoma S/37, treated with testicle extract, either fail to grow on inoculation or result in tumors of a lower growth rate than the controls. Autografts of spontaneous mouse tumors so treated show little if any effect, while the Bashford adenocarcinoma and the unattenuated S/37 are unaffected. The factor in testicle extract responsible for the retarding activity passes readily through a Berkefeld filter and is thermostable.
Development of Major Depression After Treatment for Smoking Cessation
Authors: Janice Y. Tsoh, Gary L. Humfleet, Ricardo F. Muð®¸¼, Victor I. Reus, Diane T. Hartz, Sharon M. Hall
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Case studies suggest cigarette abstinence may precipitate a major depressive episode. This study examined the incidence and predictors of major depression in the 12 months after treatment for smoking cessation. METHOD: Participants (N=304, 172 women) were recruited from two trials of smoking cessation. Both trials provided psychological group intervention, but one group received treatment with nicotine gum and the other was given nortriptyline or placebo. The incidence of major depressive episodes was identified by the Inventory to Diagnose Depression, which was administered at follow-up assessments. RESULTS: The 12-month incidence of major depression after treatment for smoking cessation was 14.1% (N=43). Multiple logistic regression analyses indicated that history of depression, baseline Beck Depression Inventory score, college education, and age at smoking initiation were significant predictors of major depression after treatment. Abstinence at the end of treatment did not significantly predict major depression. CONCLUSIONS: Patients who achieved abstinence from smoking showed a risk of developing depressive episodes similar to those who failed to achieve abstinence. As expected, patients who had a history of depression were more likely to experience depressive episodes after treatment for smoking cessation. The 12-month incidence of major depression in this study group was higher than that observed in the general population, but reasons for the elevation were not clear.
Relative Intensity of Physical Activity and Risk of Coronary Heart Disease
Authors: I-Min Lee, Howard D. Sesso, Yuko Oguma, Ralph S. Paffenbarger
Journal: Circulation (2003)

Background— Current recommendations prescribe at least moderate-intensity physical activity, requiring ≥3 METs (metabolic equivalents) for ≥30 minutes almost daily, generating ≈1000 kcal/wk. Defining intensity using an absolute scale in METs may be limited because it neglects variations in physical fitness: an activity requiring a particular MET value commands greater physical effort among less fit than more fit persons. It is unknown whether moderate-intensity exercise, relative to an individual’s capacity, is associated with reduced coronary heart disease (CHD) rates. Methods and Results— We followed 7337 men (mean age, 66 years) from 1988 to 1995. At baseline, men reported their actual activities and, using the Borg Scale, the perceived level of exertion when exercising (relative intensity). During follow-up, 551 men developed CHD. After multivariate adjustment, the relative risks of CHD among men who perceived their exercise exertion as “moderate,” “somewhat strong,” and “strong” or more intense were 0.86 (95% confidence interval, 0.66 to 1.13), 0.69 (0.51 to 0.94), and 0.72 (0.52 to 1.00), respectively ( P trend =0.02), compared with “weak” or less intense. This inverse association extended to men not fulfilling current recommendations, ie, expending &lt;1000 kcal/wk in physical activity or not engaging in activities of ≥3 METs ( P trend =0.03 and 0.007, respectively). Conclusions— There is an inverse association between relative intensity of physical activity (an individual’s perceived level of exertion) and risk of CHD, even among men not satisfying current activity recommendations. Recommendations for “moderate”-intensity physical activity may need to consider individual fitness levels instead of globally prescribing activities of ≥3 METs.
The dynamics of granuloma formation in experimental visceral leishmaniasis.
Authors: M J McElrath, H W Murray, Z A Cohn
Journal: The Journal of Experimental Medicine (1988)

We have examined the temporal sequence of events leading to the formation of hepatic granulomas after the intravenous injection of L. donovani amastigotes into BALB/c mice. Parasite ingestion by permissive Kupffer cells (KC) occurred promptly, and local KC aggregations were the foci about which granulomas were subsequently formed. Infected KC were recognized by the uptake of colloidal carbon and the expression of the macrophage-specific antigen recognized by F4/80 mAb. Peroxidase-positive granulocytes migrated rapidly and were followed by monocytes and L3T4+ T cells that enclosed the infected KC. Thereafter, Ly-2+ T cells were prominent members of the granulomatous lymphoid population. Parasites multiplied until 4 wk, and then a prompt reduction in infected cells occurred. This was associated with a sharp decline in the L3T4+ T cells of the granulomas and the maintenance of the Ly-2+ subset. In comparison, athymic nu/nu mice developed smaller, more slowly appearing granulomas that contained granulocytes and monocytes and exhibited progressive parasite replication. Upon rechallenge, the entire process was completed in 2 wk, and infected KC in the euthymic mice were never observed. We hypothesize that the effectiveness of the granulomatous response requires the destruction of parasitized host cells (KC), in a lymphokine rich environment. We further suggest that the Ly-2+ T cell serves as an important effector cell in this process, either by direct cytotoxicity or by supporting the cytotoxic potential of other cell types in the granuloma.
Multiple γ-secretase product peptides are coordinately increased in concentration in the cerebrospinal fluid of a subpopulation of sporadic Alzheimer’s disease subjects
Authors: Saori Hata, Miyako Taniguchi, Yi Piao, Takeshi Ikeuchi, Anne M Fagan, David M Holtzman, Randall Bateman, Hamid R Sohrabi, Ralph N Martins, Sam Gandy, Katsuya Urakami, Toshiharu Suzuki
Journal: Molecular Neurodegeneration (2012)

Abstract Background Alcadein α (Alc α ) is a neuronal membrane protein that colocalizes with the Alzheimer's amyloid-β precursor protein (APP). Successive cleavage of APP by β- and γ-secretases generates the aggregatable amyloid-β peptide (Aβ), while cleavage of APP or Alc α by α- and γ-secretases generates non-aggregatable p3 or p3-Alc α peptides. Aβ and p3-Alc α can be recovered from human cerebrospinal fluid (CSF). We have previously reported alternative processing of APP and Alc α in the CSF of some patients with sporadic mild cognitive impairment (MCI) and AD (SAD). Results Using the sandwich enzyme-linked immunosorbent assay (ELISA) system that detects total p3-Alc α , we determined levels of total p3-Alc α in CSF from subjects in one of four diagnostic categories (elderly controls, MCI, SAD, or other neurological disease) derived from three independent cohorts. Levels of Aβ40 correlated with levels of total p3-Alc α in all cohorts. Conclusions We confirm that Aβ40 is the most abundant Aβ species, and we propose a model in which CSF p3-Alc α can serve as a either (1) a nonaggregatable surrogate marker for γ-secretase activity; (2) as a marker for clearance of transmembrane domain peptides derived from integral protein catabolism; or (3) both. We propose the specification of an MCI/SAD endophenotype characterized by co-elevation of levels of both CSF p3-Alc α and Aβ40, and we propose that subjects in this category might be especially responsive to therapeutics aimed at modulation of γ-secretase function and/or transmembrane domain peptide clearance. These peptides may also be used to monitor the efficacy of therapeutics that target these steps in Aβ metabolis
Phase I/II Combined Chemoimmunotherapy with Carcinoembryonic Antigen–Derived HLA-A2–Restricted CAP-1 Peptide and Irinotecan, 5-Fluorouracil, and Leucovorin in Patients with Primary Metastatic Colorectal Cancer
Authors: Martin R. Weihrauch, Sascha Ansén, Elke Jurkiewicz, Caroline Geisen, Zhinan Xia, Karen S. Anderson, Edith Gracien, Manuel Schmidt, Burghardt Wittig, Volker Diehl, Juergen Wolf, Heribert Bohlen, Lee M. Nadler
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We conducted a phase I/II randomized trial to evaluate the clinical and immunologic effect of chemotherapy combined with vaccination in primary metastatic colorectal cancer patients with a carcinoembryonic antigen–derived peptide in the setting of adjuvants granulocyte macrophage colony-stimulating factor, CpG-containing DNA molecules (dSLIM), and dendritic cells. Experimental Design: HLA-A2–positive patients with confirmed newly diagnosed metastatic colorectal cancer and elevated serum carcinoembryonic antigen (CEA) were randomized to receive three cycles of standard chemotherapy (irinotecan/high-dose 5-fluorouracil/leucovorin) and vaccinations with CEA-derived CAP-1 peptide admixed with different adjuvants [CAP-1/granulocyte macrophage colony-stimulating factor/interleukin-2 (IL-2), CAP-1/dSLIM/IL-2, and CAP-1/IL-2]. After completion of chemotherapy, patients received weekly vaccinations until progression of disease. Immune assessment was done at baseline and after three cycles of combined chemoimmunotherapy. HLA-A2 tetramers complexed with the peptides CAP-1, human T-cell lymphotrophic virus type I TAX, cytomegalovirus (CMV) pp65, and EBV BMLF-1 were used for phenotypic immune assessment. IFN-γ intracellular cytokine assays were done to evaluate CTL reactivity. Results: Seventeen metastatic patients were recruited, of whom 12 completed three cycles. Therapy resulted in five complete response, one partial response, five stable disease, and six progressive disease. Six grade 1 local skin reactions and one mild systemic reaction to vaccination treatment were observed. Overall survival after a median observation time of 29 months was 17 months with a survival rate of 35% (6 of 17) at that time. Eight patients (47%) showed elevation of CAP-1–specific CTLs. Neither of the adjuvants provided superiority in eliciting CAP-1–specific immune responses. During three cycles of chemotherapy, EBV/CMV recall antigen–specific CD8+ cells decreased by an average 14%. Conclusions: The presented chemoimmunotherapy is a feasible and safe combination therapy with clinical and immunologic efficacy. Despite concurrent chemotherapy, increases in CAP-1–specific T cells were observed in 47% of patients after vaccination.
Sweet Taste Preference as a Risk Factor for Alcohol Dependence
Authors: Henry R. Kranzler, Kristen A. Sandstrom, Jeffrey Van Kirk
Journal: American Journal of Psychiatry (2001)

Previous research has found that alcoholics have a greater preference for sweet solutions than comparison subjects. This study tested the hypothesis that preference for sweet solutions is a marker for alcoholism risk.A total of 122 nonalcoholic subjects (59 men) participated. Fifty-eight subjects had a paternal history of alcoholism, and 64 did not. Each subject rated a series of sucrose solutions for intensity of sweetness and degree of preference.Subjects were able to rate accurately the relative intensity of sweetness in the sucrose solutions. Both subjects with and those without a paternal history of alcoholism preferred a 0.42-M sucrose solution, irrespective of gender.This study failed to support the hypothesis that sweet preference is a marker of alcoholism risk. The sweet preference observed previously among alcoholics may be a consequence of chronic alcohol consumption or other factors associated with heavy drinking.
Defining infertility—a systematic review of prevalence studies
Authors: S. Gurunath, Z. Pandian, Richard A. Anderson, Siladitya Bhattacharya
Journal: Human Reproduction Update (2011)

Existing definitions of infertility lack uniformity, rendering comparisons in prevalence between countries or over time problematic. The absence of an agreed definition also compromises clinical management and undermines the impact of research findings. The aim of this study was to perform a systematic review of the literature to determine how infertility has been defined in prevalence studies and to come up with suggestions for a feasible and clinically relevant definition. MEDLINE, EMBASE, CINAHL and Cochrane Database of Systematic Reviews were searched for relevant population-based prevalence studies published between 1975 and 2010. A total of 39 articles were included in the current review. The results highlight the heterogeneity of criteria used to define infertility and critical differences between demographic and epidemiological definitions. Demographers tend to define infertility as childlessness in a population of women of reproductive age, while the epidemiological definition is based on ‘trying for’ or ‘time to’ a pregnancy, generally in a population of women exposed to the risk of conception. There is considerable variation in terms of the duration of ‘trying for pregnancy’, the age of women sampled and their marital or cohabitation status. This leads to inconsistencies in determining the numerator and denominator used to calculate the prevalence of infertility. There is a need for an agreed definition for infertility. We suggest a clinically relevant definition based on the duration of trying for pregnancy coupled with female age.
Cholinesterase activity of motor end plate in human skeletal muscle
Authors: Tatsuji Namba, David Grob
Journal: Journal of Clinical Investigation (1970)

The activity and properties of cholinesterase of the motor end plate in human intercostal muscle were studied in the isolated muscle membrane. This preparation was used because cholinesterase activity of the membrane preparation was localized in the motor end plate without contamination of cholinesterase of other muscle components. Under the experimental conditions, cholinesterase in a human end plate hydrolyzed 1.21 x 10(8) molecules of acetylcholine per msec, which is smaller than hydrolysis of 2.69 x 10(8) by a motor end plate of rat intercostal muscle. Studies with cholinesterase inhibitors and specific substrates indicated that about 90% of cholinesterase of human motor endplates is acetylcholinesterase, and about 10% is pseudocholinesterase. The end plate cholinesterase had an optimal pH of 7.8 and a Michaelis-Menten constant of 4.15 mmoles/liter, and was stable at 4 degrees C for at least 4 wk. Motor end plates were estimated to contain only about 2% of the total cholinesterase activity of human intercostal muscle, compared with about 20% in rat tibialis anterior muscle. The difference is due to the lower cholinesterase activity of the motor end plate and higher cholinesterase activity of non-end plate components in human muscle than in rat muscle. The isolated muscle membrane provides a useful preparation for the study of the properties of motor end plate in human skeletal muscle.
Prevalence of allergic sensitization in the United States: Results from the National Health and Nutrition Examination Survey (NHANES) 2005-2006
Authors: Päivi M. Salo, Samuel J. Arbes, Renee Jaramillo, Agustin Calatroni, Charles H. Weir, Michelle L. Sever, Jane A. Hoppin, Kathryn M. Rose, Andrew H. Liu, Peter J. Gergen, Herman E. Mitchell, Darryl C. Zeldin
Journal: Journal of Allergy and Clinical Immunology (2014)
Diagnoses of chronic beryllium disease within cohorts of sarcoidosis patients
Authors: J. Müller-Quernheim, K. I. Gaede, E. Fireman, G. Zissel
Journal: European Respiratory Journal (2006)

An increase in chronic beryllium disease (CBD) has been suggested due to higher industrial use of beryllium alloys. Since occupational CBD is a perfect phenocopy of sarcoidosis, it might be misdiagnosed as sarcoidosis. In the current it was hypothesised that CBD exists in cohorts of sarcoidosis patients. In a prospective case study, sarcoidosis patients were evaluated for potential beryllium exposure. In those patients in whom beryllium exposure was confirmed and beryllium hypersensitivity demonstrated, the diagnosis of sarcoidosis was rejected and corrected to CBD. In 84 patients seen for re-evaluation or making a diagnosis of sarcoidosis, beryllium exposure was recognised and a diagnosis of CBD was made in 34 out of 84 patients. The time lag between clinical diagnosis of sarcoidosis and the final diagnosis of CBD ranged 0–18 yrs (median 3 yrs) and the mean (range) age at time of diagnosis of CBD was 43.9(25–80) yrs. Beryllium-contaminated workplaces causing disease encompassed a wide spectrum of industries and technical trades in which beryllium-exposure is generally not perceived as a health hazard. In conclusion, chronic beryllium disease still belongs to the spectrum of differential diagnoses of granulomatous disorders.
Reg3β Deficiency Impairs Pancreatic Tumor Growth by Skewing Macrophage Polarization
Authors: Meritxell Gironella, Carlos Calvo, Anna Fernández, Daniel Closa, Juan L. Iovanna, Joan Rosello-Catafau, Emma Folch-Puy
Journal: Cancer Research (2013)

The lectin Reg3β provides crucial protection to various tissues against inflammation, a potential risk factor for pancreatic ductal adenocarcinoma. Reg3β is also overexpressed in serum and pancreatic juice from patients with this cancer, but its function in this context remains to be elucidated. In this study, we investigated the role of Reg3β in tumor development in an orthotopic mouse model of pancreatic cancer. Reg3β deletion in mice drastically impaired pancreatic tumor growth, correlating with decreased angiogenesis and increased apoptosis of tumor cells. Moreover, Reg3β deficiency resulted in an alteration of the tumoral immune microenvironment, reflected by a decrease in the M2/M1 ratio of tumor-associated macrophages and an upregulation of CD3(+) cell infiltration. Addition of Reg3β to prestimulated RAW 264.7 or primary macrophages enhanced M2 polarization through the activation of STAT3 signaling pathway. Conditioned media from Reg3β-M2-polarized primary macrophages inhibited apoptosis and prolonged the viability of Panc02 tumor cells. Our studies reveal a novel role for Reg3β as a tumor promoter in pancreatic adenocarcinoma through the regulation of tumor stroma. Thus, inhibition of this protein may be a useful strategy in treatment of pancreatic cancer.
Association of gut inflammation with increased serum IgA class Klebsiella antibody concentrations in patients with axial ankylosing spondylitis (AS): implication for different aetiopathogenetic mechanisms for axial and peripheral AS?
Authors: O. Maki-Ikola, M. Leirisalo-Repo, U. Turunen, K. Granfors
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVES</h3> A role for <i>Klebsiella pneumoniae</i>in ankylosing spondylitis (AS) has been suggested because faecal carriage of Klebsiella and serum Klebsiella specific antibodies may be increased in this disease. This study has extended the earlier findings by comparing Klebsiella specific serum IgA class antibodies with inflammatory changes in the gut. <h3>METHODS</h3> IgA antibodies to <i>K pneumoniae, Escherichia coli, </i>and <i>Proteus mirabilis</i> in serum samples of 25 patients with AS, of eight control patients, and of 100 healthy blood donors were measured by enzyme immunoassay. Gut inflammation of the patients was studied by ileocolonoscopy. <h3>RESULTS</h3> Increased IgA antibody concentrations to<i>K pneumoniae </i>associated with gut inflammation in patients with axial form of AS. Such association was not seen in patients with peripheral form of AS. <h3>CONCLUSIONS</h3> These findings may provide further evidence for the role of <i>K pneumoniae </i>in the pathogenesis of AS. However, at least some of the patients with axial AS without gut inflammation, as well as patients with peripheral AS did not have increased <i>K pneumoniae </i>antibody concentrations, which may be regarded as evidence against the direct role of <i>K pneumoniae</i> in the pathogenesis. The aetiopathogenetic mechanisms in the axial and peripheral form of AS may be different.