tbuckley/cabot-search huggingface dataset:
A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer
Authors: Soonmyung Paik, Steven Shak, Gong Tang, Chungyeul Kim, Joffre Baker, Maureen Cronin, Frederick L. Baehner, Michael G. Walker, Drew Watson, Taesung Park, William Hiller, Edwin R. Fisher, D. Lawrence Wickerham, John Bryant, Norman Wolmark
Journal: New England Journal of Medicine (2004)

The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures.We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of 21 prospectively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative, tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14. The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospectively defined algorithm to calculate a recurrence score and to determine a risk group (low, intermediate, or high) for each patient.Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks. The proportions of patients categorized as having a low, intermediate, or high risk by the RT-PCR assay were 51, 22, and 27 percent, respectively. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk, intermediate-risk, and high-risk groups were 6.8 percent (95 percent confidence interval, 4.0 to 9.6), 14.3 percent (95 percent confidence interval, 8.3 to 20.3), and 30.5 percent (95 percent confidence interval, 23.6 to 37.4). The rate in the low-risk group was significantly lower than that in the high-risk group (P<0.001). In a multivariate Cox model, the recurrence score provided significant predictive power that was independent of age and tumor size (P<0.001). The recurrence score was also predictive of overall survival (P<0.001) and could be used as a continuous function to predict distant recurrence in individual patients.The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer.
Heparin inhibits collagenase gene expression mediated by phorbol ester-responsive element in primate arterial smooth muscle cells.
Authors: Y P Au, K F Montgomery, A W Clowes
Journal: Circulation Research (1992)

Heparin is a potent inhibitor of arterial smooth muscle cell (SMC) migration and proliferation in vivo and in vitro. We propose that heparin affects these SMC functions by interfering with either the expression or the activity of secreted proteases required for cell movement. We have reported that heparin selectively inhibits the expression of tissue-type plasminogen activator in SMCs during mitogenesis. In this study we show that the gene expression of another kind of protease, interstitial collagenase, is induced by fetal bovine serum and is also suppressed by heparin. The inhibitory effect on the induced collagenase mRNA is specific to heparin-like molecules and does not depend on the anticoagulant activity of heparin. The induction of the collagenase gene depends on the protein kinase C pathway, since it can be induced by phorbol esters such as phorbol 12-myristate 13-acetate and blocked by inhibitors such as H-7 and staurosporine. In transient transfection assays with chloramphenicol acetyltransferase constructs containing the phorbol ester-responsive element introduced into baboon SMCs, heparin inhibits transcription induced by serum or phorbol 12-myristate 13-acetate. These results support the conclusion that, in primate SMCs, interstitial collagenase gene transcription mediated by the phorbol ester-responsive element is blocked by heparin.
Orca's Survival during the Ice Age
Authors: J. Caspermeyer
Journal: Molecular Biology and Evolution (2014)

In the ocean, the killer whale rules as a top predator, feeding on everything from seals to sharks. Being at the apex of the food chain, killer whales’ geographic distribution and population size can also serve as a sentinel species regarding past and future ocean ecosystems and environmental change. In a recent study inMolecularBiologyand Evolution, Moura et al. (2014) assembled 2.23 Gb of northern hemisphere killer whale genomic data and mitochondrial DNA from 616 samples worldwide. Would the data analysis reveal patterns of past climate change that may have impacted food availability? Also, what happened to the diversity of killer whales over time during the last great ice age? From this data set, the authors used an evolutionary coalescent model to conclude that killer whales were stable in population size during most of the Pleistocene (2.5 million– 11,000 years ago) followed by a rapid decline and bottleneck during the last great period of ice age (110,000–12,000 years ago). Although most populations declined, a population off of southern Africa remained stable. Consistent with the population bottleneck, they also showed low genetic diversity, with the exception of a refuge population off the coast of South Africa. “Our data supports the idea of a population bottleneck affecting killer whales over a wide geographic range and leading to the loss of diversity,” said Moura et al. (2014) .“ The South African population stands out as an exception, which may be due to local conditions that were productive and stable over the last million years or so.” Thus, the recent ice age may have been detrimental to the ocean’s top predator and significantly affected diversity among living populations.
Overexpression of Activating Transcription Factor-2 Is Required for Tumor Growth and Progression in Mouse Skin Tumors
Authors: Paraskevi Papassava, Vassilis G. Gorgoulis, Dimitra Papaevangeliou, Spiros Vlahopoulos, Hans van Dam, Vassilis Zoumpourlis
Journal: Cancer Research (2004)

Abstract Activating transcription factor (ATF)-2 is a member of the ATF/cyclic AMP-responsive element binding protein family of transcription factors. It has been shown, in vitro, to possess growth factor-independent proliferation and transformation capacity. The information concerning the involvement of ATF-2 in carcinogenesis is rather limited. In a previous report, we showed a progressive increase in the levels of various activator protein (AP)-1 components, including phosphorylated ATF-2, in a series of mouse skin cell lines that represented developmental stages of the mouse skin carcinogenesis system. In the present study, we examined in detail the role of ATF-2 in the development of mouse skin spindle cells A5 and CarB, which correspond to the late and most aggressive stage of the mouse skin carcinogenesis model. To address this issue, we overexpressed a dominant negative form of ATF-2 in the A5 and CarB cell lines and examined their behavior in vitro and in vivo at the molecular and cellular level. The stable transfectants expressed decreased levels of phosphorylated ATF-2 and c-Jun. Subsequently, we observed that dominant negative ATF-2 affected the composition and reduced the activity of AP-1. The above biochemical changes were followed, both in vitro and in vivo in BALB/c severe combined immunodeficient mice, by suppression of the aggressive characteristics of the A5 and CarB mouse skin spindle cells. We attributed this behavior to the significant down-regulation of cyclin D1, cyclin A, and ATF-3, known AP-1 targets implicated in cell cycle control and promotion. In conclusion, our findings underscore a key regulatory role of ATF-2 in tumor growth and progression of mouse skin tumors.
Uterine-Artery Embolization versus Surgery for Symptomatic Uterine Fibroids
Authors: Richard D Edwards, Jonathan G Moss, Mary Ann Lumsden, Olivia Wu, Lilian S Murray, Sara Twaddle, Gordon D Murray
Journal: New England Journal of Medicine (2007)

The efficacy and safety of uterine-artery embolization, as compared with standard surgical methods, for the treatment of symptomatic uterine fibroids remain uncertain.
The Novel Angiogenic Inhibitor, Angiocidin, Induces Differentiation of Monocytes to Macrophages
Authors: Anita Gaurnier-Hausser, Vicki L. Rothman, Svetoslav Dimitrov, George P. Tuszynski
Journal: Cancer Research (2008)

We previously showed that angiocidin, a tumor and vascular associated protein, is a potent inhibitor of angiogenesis and tumor growth. Angiocidin is a multidomain protein that exerts its antiangiogenic activity through multiple mechanisms, including effects on cell matrix interaction. Here, we describe another activity of angiocidin that may contribute to its antitumor activity. We show that angiocidin activates monocytes to secrete a mixture of proinflammatory cytokines and induces them to differentiate into macrophage-like cells. Using the monocytic cell line THP-1, we show that angiocidin induces the cells to become adherent and phagocytic, express macrophage markers, and secrete matrix metalloproteinase-9. Microarray analysis of control and angiocidin-treated THP-1 cells revealed that angiocidin up-regulated p105/p50, p100/p52, and rel B, components of the nuclear factor-kappaB (NF-kappaB) pathway. We confirmed the microarray data and showed that angiocidin induced phosphorylation of I kappa beta, p50, and p65 and translocation of p50 and p65 to the nucleus. We also showed that angiocidin activated up-stream mediators of NF-kappaB, such as the mitogen-activated protein kinase (MAPK) pathway and phosphoinositide-3 kinase (PI3K). Blockage of NF-kappaB and MAPK activation with small molecule inhibitors completely prevented angiocidin-mediated secretion of cytokines from THP-1 cells, but did not inhibit their adhesive phenotype. Blocking PI3K inhibited both secretion of cytokines, as well as the adhesive phenotype. These data suggest that angiocidin activates monocytes to secrete cytokines and differentiates them to a macrophage-like phenotype through at least two pathways mediated by MAPK and NF-kappaB, as well as PI3K.
Helmut Drexler, MD
Authors: Victor J. Dzau, Jeffery D. Molkentin
Journal: Circulation (2009)

Helmut Drexler died suddenly while cycling in the outskirts of Hannover, Germany.Only 58 years old at the time of his death, Professor Drexler spent his life probing the biological mysteries of cardiovascular disease and pursuing potent new therapies to fight it.Thus, it is sad and sobering that this very disease appeared to have claimed his life in the end.Helmut was a dear friend and treasured collaborator to many of us, while to the greater cardiovascular community he was perhaps one of the top leaders and pioneers in translational medicine.
Prevalence of bronchial hyperresponsiveness and asthma in a rural adult population.
Authors: A J Woolcock, J K Peat, C M Salome, K Yan, S D Anderson, R E Schoeffel, G McCowage, T Killalea
Journal: Thorax (1987)

The prevalence of bronchial hyperresponsiveness in adult populations is not known. To document its prevalence and distribution and to determine the factors associated with it, a random sample of the adult population of Busselton, Western Australia, was studied. Spirometric function, bronchial responsiveness to histamine, and atopic responses to skin prick tests were measured. Respiratory symptoms were determined by questionnaire. Data were obtained from 916 subjects. Of these, 876 underwent a histamine inhalation test and bronchial hyperresponsiveness to histamine (defined as a dose of histamine provoking a 20% fall in FEV1 equal to or less than 3.9 mumol) was found in 10.5%. Another 40 subjects with poor lung function were tested with a bronchodilator and 12 were found to have bronchial hyperresponsiveness (defined as a greater than 15% increase in FEV1), making the total prevalence of bronchial hyperresponsiveness 11.4%. The prevalence of current asthma, defined as bronchial hyperresponsiveness plus symptoms consistent with asthma in the last 12 months, was 5.9%. The distribution of bronchial hyperresponsiveness in the studied population was continuous. There was a significant association between it and respiratory symptoms, atopy, smoking, and abnormal lung function (p less than 0.001 for all associations). There was no association with age, sex, or recent respiratory tract infection.
Small intestinal permeability in animals and man
Authors: C. A. Loehry, J. Kingham, J. Baker
Journal: Gut (1973)

The permeability of the human small intestine has been studied by measuring the clearance from the plasma into the intestinal lumen of substances with molecular weights ranging from 60 to 80 000. A direct relationship has been demonstrated between intestinal loss and plasma concentration and an inverse one between clearance and molecular size.The permeability of the rabbit small intestine has been studied at various levels by measuring the blood-to-lumen clearance of substances of different molecular size ranging from 60 to 40 000. It has been demonstrated that there is a progressive fall in permeability from the duodenum to the terminal ileum for all the substances studied.
Social factors associated with increases in tuberculosis notifications
Authors: K Tocque, M Regan, T Remmington, NJ Beeching, I Jamieson, Q Syed, PD Davies
Journal: European Respiratory Journal (1999)

This study assessed the contribution of immigration and deprivation to the changes in tuberculosis notifications in Liverpool over the last 20 yrs. Ethnic origin was retrospectively assigned to all named cases from 1974 to 1995. Average tuberculosis rates were calculated for the 33 council wards in Liverpool for 1981-1985 and 1991-1995. Multiple regression was used to determine the independent effects of socioeconomic and population measures from the 1981 and 1991 censuses in explaining these ward-based rates. Since 1974, there has been a steady increase in the percentage of non-Caucasian cases of tuberculosis, from 8.7% in 1975-1977, 15.1% in 1981-1983, 17.5% in 1987-1989 to 28.0% in 1993-1995. Multiple regression analysis showed that in 1981 only unemployment had a significant independent relationship with tuberculosis rates, but in 1991 two indices of deprivation and ethnicity had a significant influence. The increasing proportion of non-Caucasian tuberculosis cases, both while the number of notifications was declining before 1987 and increasing afterwards, is not necessarily consistent with the concept that immigration has influenced the recent increase. However, the fact that ethnicity now independently explains some of the council ward variations but did not in the early 1980s suggests that immigration does influence the distribution of disease within the city.
Association of Depressive Symptoms With Impaired Glucose Regulation, Screen-Detected, and Previously Known Type 2 Diabetes
Authors: Pekka Mäntyselkä, Katariina Korniloff, Timo Saaristo, Hannu Koponen, Johan Eriksson, Hannu Puolijoki, Markku Timonen, Jouko Sundvall, Hannu Kautiainen, Mauno Vanhala
Journal: Diabetes Care (2010)

OBJECTIVE To study the association between impaired glucose regulation (IGR), screen-detected type 2 diabetes, and previously known diabetes and depressive symptoms. RESEARCH DESIGN AND METHODS Altogether, 2,712 participants from three hospital districts in Finland attended a health examination. Cutoff scores ≥10 and ≥16 in the 21-item Beck Depression Inventory (BDI-21) were used for depressive symptoms. The participants were defined as having known diabetes if they reported diabetes. An oral glucose tolerance test was used to detect normal glucose regulation (NGR), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and screen-detected diabetes. The participants were defined as having IGR if they had IFG or IGT. RESULTS Prevalence of depressive symptoms, defined as a BDI-21 cutoff score ≥10, was 14.4% for those with NGR, 13.7% for those with IGR, 14.8% for those with screen-detected diabetes, and 26.4% for those with previously known diabetes. The corresponding prevalences for a cutoff score ≥16 were 3.4, 3.4, 4.2, and 7.5%, respectively. Compared with NGR and adjusted for demographic, lifestyle, and biological factors, the odds ratios for IGR, screen-detected diabetes, and previously known diabetes were 0.91 (95% CI 0.69–1.20), 0.70 (0.45–1.08), and 1.35 (0.84–2.15), respectively, for a cutoff score ≥10. For a cutoff score ≥16, the corresponding odds ratios were 1.05 (0.62–1.76), 0.87 (0.40–1.90), and 1.56 (0.69–3.50), respectively. CONCLUSIONS Participants with diagnosed diabetes had a higher prevalence of depressive symptoms than participants with NGR, IGR, and previously unknown diabetes. When potential confounding factors were included in the analysis, previously known diabetes was not significantly associated with depressive symptoms.
Guidelines for colorectal cancer screening in high risk groups
Authors: S Cairns, J H Scholefield
Journal: Gut (2002)

The British Society of Gastroenterology (BSG) and the Association of Coloproctology for Great Britain and Ireland (ACPGBI) commissioned these guidelines. The aim is to provide guidance on the appropriateness, method, and frequency of screening people with diseases known to be associated with colorectal cancer. There is increasing awareness among relatives of patients with colorectal cancer that they may be at risk from this disease and there is rising demand for screening. These guidelines are for members of gastroenterology teams, primary care physicians, purchasers of health care, and people thought to be at increased risk of colorectal cancer.
Declining Serum Total Cholesterol Levels Among US Adults
Authors: Clifford L. Johnson
Journal: JAMA (1993)

To examine the secular trend in serum total cholesterol levels of the US adult population.Nationally representative cross-sectional surveys with both an in person interview and a medical examination that included the measurement of blood lipid levels.Between 6000 and 13,000 adults aged 20 through 74 years examined in each of four separate national surveys during 1960 through 1962, 1971 through 1974, 1976 through 1980, and 1988 through 1991.Mean serum total cholesterol levels in US adults aged 20 through 74 years have consistently declined over the time period 1960 through 1991. More than half of the decline occurred during the time period 1976 through 1991. This decline occurred across the entire distribution of serum cholesterol levels and in all age-sex groups. High-density lipoprotein cholesterol and very low-density lipoprotein cholesterol levels have not changed, suggesting that the decline in total cholesterol levels is due to a decline in low-density lipoprotein cholesterol levels.These results document a continuing and substantial decline in serum cholesterol levels among US adults. They suggest that public health programs, designed to reduce cholesterol levels, are proving successful. The observed downward trend in serum cholesterol levels has coincided with a continuing decline in coronary heart disease mortality. These observations suggest that the Healthy People 2000 goal of reducing the mean serum cholesterol level of US adults to no more than 200 mg/dL (5.17 mmol/L) is attainable.
Lineage-specific expression of a T cell receptor variable gene promoter controlled by upstream sequences.
Authors: D J Diamond, F B Nelson, E L Reinherz
Journal: The Journal of Experimental Medicine (1989)

We have characterized the sequence contribution of DNA 5' of a functionally rearranged TCR promoter (V beta 8.1) on its T lineage-specific expression through the use of the chloramphenicol acetyl-transferase (CAT) reporter gene. A 230-bp fragment located 570 bp upstream of the determined transcription start site of the V beta 8.1 promoter confers a T lineage specificity of expression to a heterologous promoter. The inability of the V beta 8.1 promoter and its associated elements to function in B cells suggests the existence of a mechanism to prevent inappropriate V beta gene expression in B cells. Of considerable interest is the fact that both a B cell-specific and a nontissue-specific enhancer element were incapable of stimulating significant expression of this promoter in B cells. We discuss the implication of these results on the process of rearrangement of both Ig and TCR genes, and the differentiation of the lymphoid system.
Low pulse oximeter-measured hemoglobin oxygen saturations with hemoglobin Cheverly
Authors: Raymond J. Hohl, Alan R. Sherburne, James E. Feeley, Titus H. J. Huisman, C. Patrick Burns
Journal: American Journal of Hematology (1998)

Unexpectedly low hemoglobin oxygen saturation as determined by pulse-oximeter analysis was observed in a patient who underwent an elective surgical procedure. Specific hemoglobin derivatives such as carboxyhemoglobin, methemoglobin, and reduced hemoglobin that have been described to lower pulse-oximetry determination of oxygenation were not detected. Absorbance spectra revealed the patient's hemoglobin to be different than that obtained from two normal volunteers. High-pressure liquid chromatographic analysis of the hemoglobin showed an unknown band that comprised 15% of the patient's hemoglobin. DNA sequence analysis showed a point mutation in the second nucleotide of the 45th codon of the β-globin chain. This mutation encodes for an abnormal β-chain (β-45 Phe→Ser) that has been described as hemoglobin Cheverly. Hemoglobin Cheverly is an unstable hemoglobin that has a similar mutation as the β-42 Phe→Ser mutation seen in hemoglobin Hammersmith. Hemoglobin Hammersmith and another unstable hemoglobin, hemoglobin Köln, have previously been described to have unexpectedly low pulse-oximeter–determined oxyhemoglobin levels. That we find hemoglobin Cheverly to result in a similar phenomenon suggests that pulse-oximeter monitoring of oxygenation status may not be appropriate for the unstable hemoglobins. Low pulse-oximeter oxygenation determinations for these hemoglobins do not appear to predict clinical hypoxemia. Am. J. Hematol. 59:181–184, 1998. © 1998 Wiley-Liss, Inc.
Case Report: Occupationally Related Recurrent Varicella (Chickenpox) in a Hospital Nurse
Authors: Chih-Hung Ku, Yu-Tien Liu, David C. Christiani
Journal: Environmental Health Perspectives (2005)

Commonly accepted outcomes of varicella-zoster virus (VZV) infections include chickenpox (primary) and shingles (recurrence or latency), as well lifetime immunity against chickenpox. We report the case of a registered nurse who worked in a neurologic surgery ward in a general hospital in Taipei, Taiwan. While working there for approximately 1 year, she developed recurrent chickenpox after caring for a paraparesis patient, who had herpes zoster during hospitalization in August 2002. The varicella incubation period was 10 days, which matched the range (10-21 days). Recently negative specific serum IgM and positive specific serum IgG indicated a past VZV infection. The nurse did not get herpes zoster from the second episode of varicella on 9 August 2002 to 4 April 2005 and is now convalescing. We conclude that occupational VZV hazards exist in the health care environment and suggest testing for VZV antibody and a VZV vaccination program for susceptible health care workers. Key words: chickenpox, indirect fluroscent antibody, occupational exposure, polymerase chain reaction, shingles, Taiwan, varicella-zoster virus.