tbuckley/cabot-search huggingface dataset:
Risk Factors for Breast Cancer According to Estrogen and Progesterone Receptor Status
Authors: G. A. Colditz, B. A. Rosner, W. Y. Chen, M. D. Holmes, S. E. Hankinson
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Evaluations of epidemiologic risk factors in relation to breast cancer classified jointly by estrogen receptor (ER) and progesterone receptor (PR) status have been inconsistent. To address this issue, we conducted a prospective evaluation of risk factors for breast cancer classified according to receptor status. Methods: During 1 029 414 person-years of follow-up of 66 145 women participating in the Nurses' Health Study from 1980 through 2000, we identified 2096 incident cases of breast cancer for which information on ER/PR status was available: 1281 were ER+/PR+, 318 were ER+/PR−, 80 were ER−/PR+, and 417 were ER−/PR−. We fit a log-incidence model of breast cancer and used polychotomous logistic regression to compare coefficients for breast cancer risk factors in patients with different ER/PR status. To test for differences in risk factor odds ratios based on marginal ER/PR categories, we evaluated ER status controlling for PR status and vice versa. The predictive ability of our log-incidence model to discriminate between women who would develop ER+/PR+ breast cancer and those who would not (and similarly for ER−/PR− breast cancer) was evaluated by using receiver operator characteristic curve analysis. All statistical tests were two-sided. Results: We observed statistically significant heterogeneity among the four ER/PR categories for some risk factors (age, menopausal status, body mass index [BMI] after menopause, the one-time adverse effect of first pregnancy, and past use of postmenopausal hormones) but not for others (benign breast disease, family history of breast cancer, alcohol use, and height). The one-time adverse association of first pregnancy with incidence was present for PR− but not for PR+ tumors after controlling for ER status (P = .007). However, the association of BMI after menopause with incidence was present for PR+ but not PR− tumors (P = .005). Statistically significant differences in the incidence of ER+ and ER− tumors were seen with age, both before and after menopause (P = .003), and with past use of postmenopausal hormones (P = .01). Area under the receiver operator characteristic curve, adjusted for age, was 0.64 (95% confidence interval [CI] = 0.63 to 0.66) for ER+/PR+ tumors and 0.61 (95% CI = 0.58 to 0.64) for ER−/PR− tumors. Conclusions: Incidence rates and risk factors for breast cancer differ according to ER and PR status. Thus, to accurately estimate breast cancer risk, breast cancer cases should be divided according to the ER and PR status of the tumor.
Epithelial Na<sup>+</sup> Channel (ENaC) Expression in the Developing Normal and Abnormal Human Perinatal Lung
Authors: DAVID E. SMITH, GAIL OTULAKOWSKI, HERMAN YEGER, MARTIN POST, ERNST CUTZ, HUGH M. O'BRODOVICH
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Impaired lung epithelial Na+ channel (ENaC) activity at the time of birth results in respiratory distress. To investigate potential mechanisms, the ontogeny and cellular distribution of the α ENaC subunit mRNA expression was studied in normal, immature, and abnormal (hypoplastic) human fetal lungs using nonradioisotopic in situ hybridization. Surprisingly, α ENaC expression was detected at the embryonic stage of normal lung development (4 to 5 wk gestation) when expression was localized to the fetal lung bud epithelium. By late gestation, ENaC was expressed in the conductive and respiratory airway epithelium, serous cells, and the distal lung unit in an alveolar type II (ATII) epitheliumlike distribution. Significant α ENaC expression was found in newborn lung diseases associated with respiratory distress. One explanation is that α ENaC mRNA is constitutively expressed, and that activity is regulated, at least in part, at the post-transcriptional level. Alternative explanations are that the expression of the β or γ ENaC subunits may be impaired in certain newborn lung diseases or that alternate Na+ permeant channels or transporters are important to lung liquid absorption in humans at birth.
The impact of chromatin modifiers on the timing of locus replication in mouse embryonic stem cells
Authors: Helle F Jørgensen, Véronique Azuara, Shannon Amoils, Mikhail Spivakov, Anna Terry, Tatyana Nesterova, Bradley S Cobb, Bernard Ramsahoye, Matthias Merkenschlager, Amanda G Fisher
Journal: Genome biology (2007)

The time of locus replication during S-phase is tightly regulated and correlates with chromatin state. Embryonic stem (ES) cells have an unusual chromatin profile where many developmental regulator genes that are not yet expressed are marked by both active and repressive histone modifications. This poised or bivalent state is also characterized by locus replication in early S-phase in ES cells, while replication timing is delayed in cells with restricted developmental options. Here we used a panel of mutant mouse ES cell lines lacking important chromatin modifiers to dissect the relationship between chromatin structure and replication timing. We show that temporal control of satellite DNA replication is sensitive to loss of a variety of chromatin modifiers, including Mll, Eed, Dnmt1, Suv39h1/h2 and Dicer. The replication times of many single copy loci, including a 5 Mb contiguous region surrounding the Rex1 gene, were retained in chromatin modifier mutant ES cells, although a subset of loci were affected. This analysis demonstrates the importance of chromatin modifiers for maintaining correct replication of satellite sequences in pluripotent ES cells and highlights the sensitivity of some single copy loci to the influence of chromatin modifiers. Abundant histone acetylation is shown to correlate well with early replication. Surprisingly, loss of DNA methylation or histone methylation was tolerated by many loci, suggesting that these modifications may be less influential for the timing of euchromatin replication.
Inducible Metabolic Abnormalities During Development of Obesity
Authors: E A H Sims, E S Horton, L B Salans
Journal: Annual Review of Medicine (1971)

The attitude reflected in the above quotation from Dr. Astwood's classic address in 1962 on the Heritage of Corpulence has been the prevalent one for some years. Except in rare instances of hypothalamic injury or Cush­ ing's syndrome, the obvious positive caloric balance of the obese is blamed upon the patient and the disorder is labeled exogenous obesity. The over­ weight today are discriminated against and physicians project on them their frustration in usually not being able to effect a cure. Over recent years, however, three types of evidence have accumulated which have lead to a suspicion that there may after all be formidable inherited anatomical or bio­ chemical defects which, together with the factors in our society which pro­ mote overnutrition, lead to obesity in certain individuals. First, there is the evidence that at least some obese patients from an early age are burdened with many more than the usual quota of adipose (and other) cells. Second, when more sophisticated techniques, such as radioimmunoassay of peptide hormones, were applied to the study of biochemical changes in obesity, it was found that there were deviations from the normal range, especially in the striking hyperinsulinemia. Some of the deviations are itemized in the left-hand column of Table 1. Finally, an old and oft-refuted doctrine that the body could adapt to excess caloric intake by altering its energy metabo­ lism, the Luxuskonsumption of the early German writers, has again been brought under serious consideration. It thus becomes more difficult to attrib­ ute obesity to a simple behavioral disorder. The obvious question arises, however, as to whether the derangements observed are the consequences of the obesity or part of the cause.
Muscle soreness, swelling, stiffness and strength loss after intense eccentric exercise.
Authors: M J Cleak, R G Eston
Journal: British Journal of Sports Medicine (1992)

High-intensity eccentric contractions induce performance decrements and delayed onset muscle soreness. The purpose of this investigation was to study the magnitude and time course of such decrements and their interrelationships in 26 young women of mean(s.d.) age 21.4(3.3) years. Subjects performed 70 maximal eccentric contractions of the elbow flexors on a pulley system, specially designed for the study. The non-exercised arm acted as the control. Measures of soreness, tenderness, swelling (SW), relaxed elbow joint angle (RANG) and isometric strength (STR) were taken before exercise, immediately after exercise (AE), analysis of variance and at 24-h intervals for 11 days. There were significant (P &lt; 0.01, analysis of variance) changes in all factors. Peak effects were observed between 24 and 96 h AE. With the exception of STR, which remained lower (P &lt; 0.01), all variables returned to baseline levels by day 11. A non-significant correlation between pain and STR indicated that pain was not a major factor in strength loss. Also, although no pain was evident, RANG was decreased immediately AE. There was no relationship between SW, RANG and pain. The prolonged nature of these symptoms indicates that repair to damaged soft tissue is a slow process. Strength loss is considered particularly important as it continues when protective pain and tenderness have disappeared. This has implications for the therapeutic management of patients with myopathologies and those receiving eccentric exercise for rehabilitation.
Deficient antigen-presenting cell function in multiple genetic complementation groups of type II bare lymphocyte syndrome.
Authors: S Kovats, G T Nepom, M Coleman, B Nepom, W W Kwok, J S Blum
Journal: Journal of Clinical Investigation (1995)

The absence of HLA class II gene expression in type II bare lymphocyte syndrome (BLS) results from defective transcriptional activation of class II histocompatibility genes. Genetic studies have revealed that distinct defects in multiple trans-acting factors result in the immunodeficient BLS phenotype. We studied antigen-presenting cell (APC) function in DR-transfected BLS cells derived from multiple complementation groups. Each BLS cell line displayed the same defective APC phenotype: an inability to mediate class II-restricted presentation of exogenous protein antigens, and structurally altered class II alpha beta dimers. Expression of the HLA class II-like genes DMA and DMB, previously implicated in antigen presentation, was reduced or absent in the BLS cells. Fusion of BLS cells with cell line 721.174, which has a genomic deletion of HLA class II genes, coordinately restores class II structural gene and DM gene expression and a wild-type APC phenotype. Thus each of the molecular defects that silences class II structural gene transcription also results in a defective APC phenotype, providing strong evidence for coregulation of these two functionally linked pathways.
Renal Vein Thrombosis
Authors: J T Harrington, J P Kassirer
Journal: Annual Review of Medicine (1982)

Renal vein thrombosis (R VT) occurs in several dis,parate settings: as an extension of clots in the vena cava, as a consequence of invasion of the renal veins by tumor, as a complication of various renal diseases, and, in children, as a consequence of severe dehydration (1-7). In this review we focus exclusively on the association of renal vein thrombosis and renal disease, particularly the nephrotic syndrome.
Reply to A. Garcia et al
Authors: Sao Jiralerspong, Ana M. Gonzalez-Angulo
Journal: Journal of Clinical Oncology (2009)

We thank Garcia and Tisman for their interesting comments regarding our manuscript. We agree that it is generally accepted that metformin is associated with lowering of serum vitamin B12 (cobalamin) levels and therefore may predispose to B12 deficiency. 2-5 The Tisman group has recently reported in a small study that holotranscobalamin was decreased in patients receiving chemotherapy, presumably related to chemotherapy-induced GI tract damage causing decreased B12 absorption. 6 So it is possible that some of the diabetic patients in our study may have had B12 deficiency secondary to metformin use and/or receiving chemotherapy. We have no data on this, as neither serum B12 nor related B12 deficiency markers (homocysteine, methylmalonic acid, holotranscobalamin) were measured in our study. The idea of holotranscobalamin, the serum protein carrier of tissue bioavailable B12, as a marker of B12 deficiency is appealing, but we note that the clinically established laboratory parameters of B12 deficiency remain B12 itself and the metabolites homocysteine and methylmalonic acid. There is evidence that B12 deficiency may have antiproliferative effects in tumor cells. The best studied example is nitrous oxide. This anesthetic induces B12 deficiency by preventing cobalamin reduction to the active cobalt(I) state, and thereby inhibits the methylcobalamindependent methionine synthase. Inhibition of methionine synthase is expected to lead to inhibition of cell proliferation, as this enzyme is necessary for DNA synthesis. There is evidence that nitrous oxide causes bone marrow suppression and has antiproliferative effects in leukemia, as discussed by Garcia and Tisman. Inhibition of other enzymes involved in folate metabolism should lead to additive or synergistic effects on cell proliferation, and this appears to be true for nitrous oxide in combination with, for instance, methotrexate or fluorouracil. We note that many of the patients in our study received fluorouracil as part of their chemotherapy. If B12 deficiency does indeed mediate a significant proportion of metformin’s antitumor activity, it would be desirable to separate this beneficial effect of B12 deficiency from its negative effects. Prominent among the latter are megaloblastic anemia and neurologic deficits, which also likely derive from inhibition of methionine synthase.
O-GlcNAc Transferase Integrates Metabolic Pathways to Regulate the Stability of c-MYC in Human Prostate Cancer Cells
Authors: Harri M. Itkonen, Sarah Minner, Ingrid J. Guldvik, Mareike Julia Sandmann, Maria Christina Tsourlakis, Viktor Berge, Aud Svindland, Thorsten Schlomm, Ian G. Mills
Journal: Cancer Research (2013)

Metabolic disruptions that occur widely in cancers offer an attractive focus for generalized treatment strategies. The hexosamine biosynthetic pathway (HBP) senses metabolic status and produces an essential substrate for O-linked β-N-acetylglucosamine transferase (OGT), which glycosylates and thereby modulates the function of its target proteins. Here, we report that the HBP is activated in prostate cancer cells and that OGT is a central regulator of c-Myc stability in this setting. HBP genes were overexpressed in human prostate cancers and androgen regulated in cultured human cancer cell lines. Immunohistochemical analysis of human specimens (n = 1987) established that OGT is upregulated at the protein level and that its expression correlates with high Gleason score, pT and pN stages, and biochemical recurrence. RNA interference-mediated siliencing or pharmacologic inhibition of OGT was sufficient to decrease prostate cancer cell growth. Microarray profiling showed that the principal effects of OGT inhibition in prostate cancer cells were related to cell-cycle progression and DNA replication. In particular, c-MYC was identified as a candidate upstream regulator of OGT target genes and OGT inhibition elicited a dose-dependent decrease in the levels of c-MYC protein but not c-MYC mRNA in cell lines. Supporting this relationship, expression of c-MYC and OGT was tightly correlated in human prostate cancer samples (n = 1306). Our findings identify HBP as a modulator of prostate cancer growth and c-MYC as a key target of OGT function in prostate cancer cells.
Principles of Preventive Mental Health Programs for Ethnic Minority Populations: The Acculturation of Puerto Ricans to the United States
Authors: RAQUEL E. COHEN
Journal: American Journal of Psychiatry (1972)

Differences in value orientation cause serious adaptation problems in both the Puerto Rican migrant and in the human and social institutions responsible for his education, employment, health, and recreation. The author discusses methods and techniques by which a mental health professional can intervene in this adaptation process and design mental health services in harmony with the value orientation of the population.
B-Type Natriuretic Peptide and Prognosis in Heart Failure Patients With Preserved and Reduced Ejection Fraction
Authors: Dirk J. van Veldhuisen, Gerard C.M. Linssen, Tiny Jaarsma, Wiek H. van Gilst, Arno W. Hoes, Jan G.P. Tijssen, Walter J. Paulus, Adriaan A. Voors, Hans L. Hillege
Journal: Journal of the American College of Cardiology (2013)
A biased survey and interpretation of the nature–nurture literature
Authors: Françoys Gagné
Journal: Behavioral and Brain Sciences (1998)

This commentary samples some of the major bodies of counterevidence omitted by Howe et al., including the strong relationship between IQ and academic excellence, the limited effects of early stimulation programs, and the measurement of musical aptitudes. The authors' selective review and analysis of the surveyed literature, especially studies of prodigies and in behavioral genetics, is discussed.
USE OF THE CHADS2 AND CHA2DS2-VASC SCORE IN JAPANESE PATIENTS WITH ATRIAL FIBRILLATION: A SUB-ANALYSIS OF THE JAPAN THROMBOSIS REGISTRY FOR ATRIAL FIBRILLATION, CORONARY OR CEREBROVASCULAR EVENTS (J-TRACE)
Authors: Eri Toda, Gregory YH Lip, Shinichiro Uchiyama, Kazyuyuki Shimada, Hideki Origasa, Hiroyuki Kobayashi, Akio Kawamura, Kazuo Kitagawa, Takehiko Nagao, Yasuo Ikeda, Shinya Goto
Journal: Journal of the American College of Cardiology (2012)
Semiquantitative Culture Analysis during Therapy for <i>Mycobacterium avium</i> Complex Lung Disease
Authors: David E. Griffith, Jennifer Adjemian, Barbara A. Brown-Elliott, Julie V. Philley, D. Rebecca Prevots, Christopher Gaston, Kenneth N. Olivier, Richard J. Wallace
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Microbiologically based criteria such as sputum culture conversion to negative have traditionally been used to define treatment success for mycobacterial diseases. There are, however, limited data regarding whether nontuberculous mycobacterial sputum culture conversion or semiquantitative culture analysis correlates with subjective or nonmicrobiologic objective indices of treatment response.To determine whether a semiquantitative mycobacterial culture scale correlated with clinical disease status and was predictive of long-term sputum mycobacterial culture conversion to negative in a cohort of patients with nodular/bronchiectatic Mycobacterium avium complex lung disease undergoing therapy.One hundred and eighty patients undergoing standard macrolide-based therapy for M. avium complex lung disease were monitored at standard frequent intervals with symptomatic, radiographic, and microbiologic data collected, including semiquantitative mycobacterial culture analysis. Analyses were used to evaluate clinical and microbiologic predictors of long-term sputum conversion to culture negative.After 12 months of therapy, 148 (82%) patients had sputum conversion to culture negative. Baseline semiquantitative sputum culture scores did not differ between patients with sputum conversion and those without. The change in sputum culture semiquantitative score from baseline to Month 3 was highly predictive of subsequent sputum long-term conversion status indicative of treatment success, as was improvement in cough, and especially early radiographic improvement.Early semiquantitative sputum agar plate culture results can be used to predict symptomatic and radiographic improvement as well as long-term sputum culture conversion to negative in this population. We suggest that semiquantitative sputum culture scores can be a useful tool for evaluating new nontuberculous mycobacterial lung disease therapies.
Targeted versus Universal Decolonization to Prevent ICU Infection
Authors: Susan S. Huang, Edward Septimus, Ken Kleinman, Julia Moody, Jason Hickok, Taliser R. Avery, Julie Lankiewicz, Adrijana Gombosev, Leah Terpstra, Fallon Hartford, Mary K. Hayden, John A. Jernigan, Robert A. Weinstein, Victoria J. Fraser, Katherine Haffenreffer, Eric Cui, Rebecca E. Kaganov, Karen Lolans, Jonathan B. Perlin, Richard Platt
Journal: New England Journal of Medicine (2013)

Both targeted decolonization and universal decolonization of patients in intensive care units (ICUs) are candidate strategies to prevent health care–associated infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA).
Dysregulation of interferon regulatory factors impairs the expression of immunostimulatory molecules in hepatitis C virus genotype 1-infected hepatocytes
Authors: Esther Larrea, Jose-I Riezu-Boj, Rafael Aldabe, Laura Guembe, Itziar Echeverria, Anangi Balasiddaiah, Pablo Gastaminza, María Pilar Civeira, Pablo Sarobe, Jesus Prieto
Journal: Gut (2013)

A double-blind test to compare IV aminophylline with salbutamol in the treatment of acute, uncontrolled asthma showed that both drugs were equally effective during the first 24 hours. Salbutamol caused a relative tachycardia. Hydrocortisone was given after 2 hours, but did not appear to affect the rate of recovery.
Lifestyle Factors in Cancer Survivorship
Authors: Jennifer Ligibel
Journal: Journal of Clinical Oncology (2012)

Lifestyle factors have been linked to the risk of developing many common malignancies and, increasingly, to prognosis. Observational evidence has shown a relationship between so-called energy balance factors (ie, diet, physical activity, and body weight) and risk of cancer recurrence and mortality in cancers of the breast, prostate, colon and, perhaps, other cancers. Interventional work has shown that individuals who make favorable changes in these lifestyle factors after cancer diagnosis feel better, experience less fatigue, and may possibly even decrease risk of cancer recurrence. Other lifestyle behaviors, such as smoking and alcohol consumption, have also been linked to the development of common cancers and may have important health consequences for cancer survivors. This article reviews the evidence that links lifestyle factors to cancer outcomes, provides clinical recommendations for cancer survivors, and describes future directions for lifestyle research in cancer survivors.
Respiratory and Limb Muscle Function in Lung Allograft Recipients
Authors: JOÃO G. PANTOJA, FRANCISCO H. ANDRADE, DOBRIVOJE S. STOKIĆ, ADAANI E. FROST, WILLIAM L. ESCHENBACHER, MICHAEL B. REID
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Lung transplantation recipients have reduced exercise capacity despite normal resting pulmonary and hemodynamic function. The limiting factor may be contractile dysfunction of skeletal muscle. To test this postulate, we measured limb and respiratory muscle function in nine clinically stable lung allograft recipients (six men and three women, aged 30 to 65 yr, at 5 to 102 mo after transplantation) with reduced exercise capacity. Respiratory muscle strength was tested by measuring maximal inspiratory and expiratory pressure (MIP and MEP, respectively). Ankle dorsiflexor muscle strength was measured during maximal voluntary contraction (MVC). In a subset of six recipients, we also measured contractile properties and fatigue characteristics of the tibialis anterior muscle, using electrical stimulation of the motor point. Data were compared with values from age- and sex-matched control subjects. MIP values of transplant recipients did not differ from control values; however, MEP was blunted by 30% relative to control (p < 0.05), and MVC was decreased by 39% (p < 0.05). The force–frequency relationships and fatigue characteristics of the tibialis anterior were not different between the patient and control groups. We conclude that stable lung allograft recipients experience expiratory and lower limb weakness that may contribute to exercise intolerance.