tbuckley/cabot-search huggingface dataset:
Individualized Survival Curves Improve Satisfaction With Cancer Risk Management Decisions in Women With <i>BRCA1/2</i> Mutations
Authors: Katrina Armstrong, Barbara Weber, Peter A. Ubel, Nikki Peters, John Holmes, J. Sanford Schwartz
Journal: Journal of Clinical Oncology (2005)

Women with BRCA1/2 mutations are faced with complex decisions about breast and ovarian cancer risk management. This study was conducted to determine the effect of a tailored decision support system (DSS) that provides individualized survival and cancer incidence curves specific to expected outcomes of alternative management strategies.This was a double-blind, randomized controlled trial of 32 women with BRCA1/2 mutations. Primary outcome measures were decision satisfaction, cancer anxiety, perceptions of cancer risk given alternative management strategies, and management decisions.Twenty-seven women completed a 6-week follow-up. Women in the intervention arm (n = 13) reported significantly higher decision satisfaction at follow-up than women in the control arm (n = 14; adjusted mean difference, 9.7; P < .0005). The effect of the DSS was greater among women with low cancer anxiety at baseline than women with high cancer anxiety at baseline (P = .01 for interaction). However, the DSS did not significantly alter cancer anxiety at follow-up, perceptions of cancer risk given alternative management strategies, or management decisions.The presentation of individualized survival and incidence curves for alternative management options improves satisfaction about cancer risk management decisions among women with BRCA1/2 mutations without increasing anxiety or changing management decisions. The benefit of the DSS is greatest among women with relatively low cancer-related anxiety at baseline.
Aberrant Brain Activation During a Working Memory Task in Psychotic Major Depression
Authors: Amy Garrett, Ryan Kelly, Rowena Gomez, Jennifer Keller, Alan F. Schatzberg, Allan L. Reiss
Journal: American Journal of Psychiatry (2010)

The authors sought to better understand the neural circuitry associated with working memory deficits in psychotic major depression by examining brain function during an N-back task.Study subjects were 16 patients with psychotic major depression, 15 patients with nonpsychotic major depression, and 19 healthy comparison subjects. Functional MRI data were collected while participants responded to letter stimuli that were repeated from the previous trial (1-back) or the one before that (2-back).Relative to the healthy comparison group, both the psychotic and nonpsychotic major depression groups had significantly greater activation in the right parahippocampal gyrus during the 2-back task, and the psychotic major depression group showed this overactivation during the 1-back task as well. The nonpsychotic major depression group showed significantly lower activation than other groups in the right dorsolateral prefrontal cortex and greater activation than the healthy comparison group in the superior occipital cortex. The psychotic major depression group was unique in showing greater activation than both other groups in the right temporoparietal junction, a cluster that also demonstrated connectivity with activation in the left prefrontal cortex.The psychotic major depression group showed aberrant parahippocampal activation at a lower demand level than observed in nonpsychotic major depression. While the nonpsychotic major depression group showed abnormalities in frontal executive regions, the psychotic major depression group showed abnormalities in temporoparietal regions associated with orienting to unexpected stimuli. Considering the functional connectivity of this cluster with left dorsolateral prefrontal cortex regions, these findings may reflect neural compensation for sensory gating deficits in psychotic major depression.
A PRISONER OF WAR SYNDROME: APATHY AS A REACTION TO SEVERE STRESS
Authors: HARVEY D. STRASSMAN, MARGARET B. THALER, EDGAR H. SCHEIN
Journal: American Journal of Psychiatry (1956)

We have pointed out that one defensive adjustment of POW's to stress is withdrawal. If the stresses are not too severe the person will withdraw physically if possible, or in any case will refuse to allow himself to become involved with the environment to as great an extent as possible. Certain kinds of overt behavior will be inhibited and most emotional responses will be suppressed. If the environment is severely stressful and physically depriving as well, the individual may regress into a more complete withdrawal and adopt a maladaptive state of dependency in which he ceases to take care of himself even to the point of death. We have labelled this type of defense "apathy" and distinguish it from states like catatonic stupor, or depression. "Apathy" appears not to be a single absolute reaction, but a syndrome which can vary markedly in degree. One major symptom in the syndrome is reduced or modulated affect, but only in extreme cases can one speak of true apathy or affectlessness. Other symptoms are listlessness, uncommunicativeness, lack of spontaneity, indifference, slowed reactions, lack of enthusiasm, and lack of initiative. It is important to note that underlying the overt lack of emotional spontaneity may lie great quantities of pent-up feelings, and that these will continue to be a problem to the individual when he is no longer in the environment that produced the "apathy syndrome." The apathy syndrome serves to maintain personality integration in the face of severe reality and psychological stresses.
Tumoral Lymphocytic Infiltration and Expression of the Chemokine CXCL10 in Breast Cancers from the Ontario Familial Breast Cancer Registry
Authors: Anna Marie Mulligan, Irene Raitman, Linda Feeley, Dushanthi Pinnaduwage, Linh T. Nguyen, Frances P. O'Malley, Pamela S. Ohashi, Irene L. Andrulis
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Breast carcinomas, including basal and hereditary cases, often present with a prominent tumoral lymphocytic infiltrate. Chemokines could play a role in attracting these cells and contribute to tumor progression. We explored tumoral expression of CXCL10 and determined the relationship between CXCL10 and lymphocytic infiltrate in a cohort of breast cancers. Experimental Design: Using tissue microarrays of 364 breast tumors, we evaluated expression of CXCL10 and its receptor, CXCR3, in relation to histopathologic features, biomarkers, and lymphocyte markers. In addition, we overexpressed CXCL10 and CXCR3 in MCF7 breast cancer cells and monitored T-lymphocyte migration and invasion. Results: Forty-five percent of tumors expressed CXCL10, and a significant association was found with CXCR3 and lymphocytic infiltrate. Further characterization of the lymphocytic infiltrate revealed an association with CXCL10 expression for peritumoral CD4+ and CD8+ lymphocytes. CD8+ intratumoral lymphocytes, FOXP3+ regulatory T cells (Tregs), and T-BET+ TH1 cells were associated with BRCA1 and basal tumors. Conditioned media from MCF7 cells overexpressing both CXCL10 and CXCR3 increased T-lymphocyte migration and invasion. Conclusions: Our findings suggest that CXCL10 may act in a paracrine manner, affecting the tumor microenvironment, and in an autocrine manner, acting on the tumor cells themselves and may play a role in tumor invasiveness and progression. The CXCL10-CXCR3 axis can serve as a potential target in BRCA1 and basal breast cancers, which present with a prominent lymphocytic infiltrate and a poor prognosis. Clin Cancer Res; 19(2); 336–46. ©2012 AACR.
2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease
Authors: Stephan D. Fihn, James C. Blankenship, Karen P. Alexander, John A. Bittl, John G. Byrne, Barbara J. Fletcher, Gregg C. Fonarow, Richard A. Lange, Glenn N. Levine, Thomas M. Maddox, Srihari S. Naidu, E. Magnus Ohman, Peter K. Smith
Journal: Circulation (2014)
An anticoagulant dermatan sulfate proteoglycan circulates in the pregnant woman and her fetus.
Authors: M Andrew, L Mitchell, L Berry, B Paes, M Delorme, F Ofosu, R Burrows, B Khambalia
Journal: Journal of Clinical Investigation (1992)

Investigation of the in vitro ability of plasma from pregnant women to inhibit exogenous thrombin (25 nM) demonstrated that heparin cofactor II inhibited more thrombin (3.0 +/- 0.7 nM, mean +/- SD) than plasma from women 3-5 d postpartum (1.9 +/- 0.5 nM) or plasma from nonpregnant adults (1.5 +/- 0.4 nM). Levels of heparin cofactor II were only slightly increased over normal in both pregnant and postpartum women and did not account for the observed increase in thrombin bound to heparin cofactor II. Assay of pregnancy plasma for dermatan sulfate anticoagulant activity demonstrated the presence of activity equivalent to 0.23 +/- 0.02 micrograms/ml of porcine mucosal dermatan sulfate. This activity could not be demonstrated in normal adult plasma or plasma from women on the contraceptive pill. The mass of dermatan sulfate in pregnancy and umbilical cord plasmas was increased over adult control plasma by 0.20 micrograms/ml (53%) and 0.29 micrograms/ml (76%), respectively. The glycosaminoglycan-containing fraction of plasma was isolated and an assay for anticoagulant dermatan sulfate confirmed its presence in both pregnancy and cord plasmas but minimal activity in adult plasma. Gel chromatography of isolated fractions from both pregnancy and cord plasmas revealed a polydisperse, active species with apparent Mr 150,000 D. Reductive elimination decreased the apparent Mr of the active species on gel chromatography to 31,000 D for cord and 21,000 D for pregnancy products. This confirmed the presence of an anticoagulant active dermatan sulfate proteoglycan circulating in the plasmas of pregnant women at term and fetuses at delivery.
Randomised aspirin assignment and risk of adult-onset asthma in the Women’s Health Study
Authors: T Kurth, R G Barr, J M Gaziano, J E Buring
Journal: Thorax (2008)

Randomised data in men show a small but significant reduction in the risk of adult-onset asthma among those given aspirin. The results from an observational study in women suggest that frequent use of aspirin decreases the risk of adult-onset asthma, but randomised data in women are lacking. A study was undertaken to test the effect of 100 mg aspirin or placebo on alternate days on the risk of adult-onset asthma in the Women's Health Study.A randomised, double-blind, placebo-controlled clinical trial of aspirin and vitamin E was performed in apparently healthy women with no indication or contraindication to aspirin therapy and no history of asthma at study entry. Female health professionals self-reported an asthma diagnosis on yearly questionnaires.Among 37 270 women with no reported history of asthma prior to randomisation and during 10 years of follow-up, there were 872 new cases diagnosed with asthma in the aspirin group and 963 in the placebo group (hazard ratio 0.90; 95% CI 0.82 to 0.99; p = 0.027). This apparent 10% lower relative risk of incident adult-onset asthma among those assigned to aspirin was significantly modified by body mass index, with no effect in women with a body mass index of >/=30 kg/m2. The effect of aspirin on adult-onset asthma was not significantly modified by age, smoking status, exercise levels, postmenopausal hormone use or randomised vitamin E assignment.In this large randomised clinical trial of apparently healthy adult women, administration of 100 mg aspirin on alternate days reduced the relative risk of a newly reported diagnosis of asthma.
Comparison of Diabetes Control Among Haitians, African Americans, and Non-Hispanic Whites in an Urban Safety-Net Hospital
Authors: Varsha G. Vimalananda, James L. Rosenzweig, Howard J. Cabral, Michele M. David, Karen E. Lasser
Journal: Diabetes Care (2010)

OBJECTIVE To compare diabetes care and outcomes among Haitians, African Americans, and non-Hispanic whites. RESEARCH DESIGN AND METHODS We analyzed data from 715 Haitian, 1,472 African American, and 466 non-Hispanic white adults with diabetes using χ2 testing and multiple logistic regression. RESULTS Haitians had a higher mean A1C than African Americans (8.2 ± 1.9 vs. 7.7 ± 2.0%) and non-Hispanic whites (7.5 ± 1.7%) (both P &amp;lt; 0.0001). There was no difference in completion of process measures. Haitians were more likely than non-Hispanic whites to have elevated LDL cholesterol or blood pressure. Macrovascular complications were fewer among Haitians than African Americans (adjusted odds ratio 0.35 [95% CI 0.23–0.55]), as were microvascular complications (0.56 [0.41–0.76]). Haitians also had fewer macrovascular (0.32 [0.20–0.50]) and microvascular (0.55 [0.39–0.79]) complications than non-Hispanic whites. CONCLUSIONS Haitians have worse glycemic control than African Americans or non-Hispanic whites. Future research and interventions to improve diabetes care should target Haitians as a distinct racial/ethnic group.
Elevation of <i>N</i>-(Carboxymethyl)valine Residue in Hemoglobin of Diabetic Patients
Authors: Tomonori Uchimura, Kazushi Nakano, Teruto Hashiguchi, Hisahiko Iwamoto, Keisuke Miura, Yoshimichi Yoshimura, Naohiro Hanyu, Koichiro Hirata, Misturu Imakuma, Yoshihiro Motomiya, Ikuro Maruyama
Journal: Diabetes Care (2001)

OBJECTIVE—Advanced glycation end products (AGEs) are a risk factor for diabetic complications. We have developed an assay method for N-(carboxymethyl)valine (CMV) of the hemoglobin (CMV-Hb), which is an AGE generated from HbA1c. Herein, we describe the clinical utility of CMV-Hb measurement for the diagnosis of diabetic nephropathy. RESEARCH DESIGN AND METHODS—BALB/c mice were immunized with carboxymethylated Hb and monoclonal antibody raised against CMV-Hb. This antibody was characterized by a surface plasmon resonance. We developed a latex immunoassay using the antibody and measured CMV-Hb from erythrocytes in type 2 diabetic patients and healthy control subjects (age 64.6 ± 12.0 vs. 61.1 ± 13.2 years, NS; HbA1c 6.9 ± 1.5 vs. 5.2 ± 0.4%, P &amp;lt; 0.0001). RESULTS—A monoclonal antibody against CMV-Hb β-chain NH2-terminal and an assay method for measurement for CMV-Hb were both developed in our laboratory. CMV-Hb levels were significantly greater in the diabetic patients than in the control subjects (18.2 ± 6.9 vs. 12.7 ± 6.9 pmol CMV/mg Hb, P &amp;lt; 0.0001). No correlation was found between CMV-Hb and HbA1c or CMV-Hb and glycated albumin. Levels of CMV-Hb increased as the diabetic nephropathy progressed. CONCLUSIONS—We established an assay method for CMV-Hb and confirmed the presence of CMV-Hb in circulating erythrocytes. CMV-Hb was more prevalent in diabetic patients than in healthy subjects. Furthermore, it was significantly higher in patients with diabetic nephropathy, suggesting that the presence of CMV-Hb may be a valuable marker for the progression of diabetic nephropathy.
RECEPTOR-MEDIATED ENDOCYTOSIS OF COBALAMIN (VITAMIN B<sub>12</sub>)
Authors: Bellur Seetharam
Journal: Annual Review of Nutrition (1999)

▪ Abstract Dietary cobalamin (Cbl) (vitamin B 12 ) is utilized as methyl-Cbl and the coenzyme 5′-deoxyadenosyl Cbl by cells of the body that have the enzymes methionine synthase and methyl malonyl CoA mutase, which convert homocysteine to methionine and methyl malonyl CoA to succinyl CoA, respectively. Prior to conversions and utilizations as the active alkyl forms of Cbl, dietary Cbl is absorbed and transported across cellular plasma membranes by two receptor-mediated events. First, dietary and biliary Cbl bound to gastric intrinsic factor (IF) presented apically to the ileal absorptive enterocytes is transported to the circulation by receptor-mediated endocytosis via apically expressed IF–Cbl receptor. Second, Cbl bound to plasma transcobalamin (TC) II is taken up from the circulation by all cells via a TC II receptor expressed in the plasma membrane of these cells, and in polarized cells via a TC II receptor expressed in the basolateral membranes. This review updates recent work and focuses on (a) the molecular and cellular aspects of Cbl binding protein ligands, IF and TC II, and their cell-surface receptors, IF–Cbl receptor and TC II receptor; (b) the cellular sorting pathways of internalized Cbl bound to IF and TC II in polarized epithelial cells; and (c) the absorption and transport disorders that cause Cbl deficiency.
Acute Hepatitis Associated with the Chinese Herbal Product Jin Bu Huan
Authors: Graham M. Woolf
Journal: Annals of Internal Medicine (1994)

Objective: To describe the hepatotoxicity associated with ingestion of the Chinese herbal product Jin Bu Huan Anodyne Tablets (Lycopodium serratum) and to propose possible mechanisms of injury. Design: Retrospective analysis. Setting: Academic hepatology units and private practice facilities. Patients: Seven previously healthy patients. Measurements: Clinical, laboratory, radiologic, and histologic studies. Results: Acute hepatitis occurred after a mean of 20 weeks (range, 7 to 52 weeks) of Jin Bu Huan ingestion and resolved in six patients within a mean of 8 weeks (range, 2 to 30 weeks); another patient is currently improving. Hepatitis was associated with symptoms of fever, fatigue, nausea, pruritus, and abdominal pain and with signs of jaundice and hepatomegaly. Biopsy specimens showed that one patient had hepatitis with eosinophils (consistent with a drug reaction) and the other had mild hepatitis, moderate fibrosis, and microvesicular steatosis. Decreasing the Jin Bu Huan dose in one patient improved liver test results. Reusing Jin Bu Huan in two other patients caused abrupt recrudescence of hepatitis. Conclusion: Jin Bu Huan can cause liver injury. Although the hepatotoxic mechanisms are not defined, they may include hypersensitive or idiosyncratic reactions or direct toxicity to active metabolites. Hepatotoxicity caused by herbal products underscores the importance of national surveillance programs and quality control of the manufacture of these products.
Clinical value of CYFRA 21.1, carcinoembryonic antigen, neurone-specific enolase, tissue polypeptide specific antigen and tissue polypeptide antigen in the diagnosis of lung cancer
Authors: J Bates, R Rutherford, M Divilly, J Finn, H Grimes, I O'Muircheartaigh, JJ Gilmartin
Journal: European Respiratory Journal (1997)

In this study we looked at what useful information cytokeratin fragment detected by antibodies BM 19-21 and KS 19-1 (CYFRA 21.1), carcinoembryonic antigen (CEA), neurone-specific enolase (NSE), tissue polypeptide specific antigen (TPS), and tissue polypeptide antigen (TPA) gave when measured prospectively. All patients who were suspected of having lung cancer and who underwent diagnostic bronchoscopy in this hospital between July 1994 and May 1995 were included in the study. Of 184 patients, 87 were subsequently found to have intrathoracic malignancy, 93 were found to have benign lung disease and four were lost to follow-up. CYFRA 21.1 was the most efficient marker in differentiating benign from malignant disease, with a sensitivity of 54% and a positive predictive value of 96%. Thirty seven patients who had a negative bronchoscopy subsequently turned out to have malignant disease. Either CYFRA 21.1 or CEA was elevated in 26 (70%) of such patients. Multivariate analysis showed that only CYFRA 21.1 and CEA contributed significantly to the discriminatory power of the data. We conclude that measurement of cytokeratin fragment detected by antibodies BM 19-21 and KS 19-1 and carcinoembryonic antigen at the time of bronchoscopy significantly increased the diagnostic yield in this population and was especially useful in those patients in whom tumour biopsy was not possible at bronchoscopy.
Tricellulin deficiency affects tight junction architecture and cochlear hair cells
Authors: Gowri Nayak, Sue I. Lee, Rizwan Yousaf, Stephanie E. Edelmann, Claire Trincot, Christina M. Van Itallie, Ghanshyam P. Sinha, Maria Rafeeq, Sherri M. Jones, Inna A. Belyantseva, James M. Anderson, Andrew Forge, Gregory I. Frolenkov, Saima Riazuddin
Journal: Journal of Clinical Investigation (2013)

The two compositionally distinct extracellular cochlear fluids, endolymph and perilymph, are separated by tight junctions that outline the scala media and reticular lamina. Mutations in TRIC (also known as MARVELD2), which encodes a tricellular tight junction protein known as tricellulin, lead to nonsyndromic hearing loss (DFNB49). We generated a knockin mouse that carries a mutation orthologous to the TRIC coding mutation linked to DFNB49 hearing loss in humans. Tricellulin was absent from the tricellular junctions in the inner ear epithelia of the mutant animals, which developed rapidly progressing hearing loss accompanied by loss of mechanosensory cochlear hair cells, while the endocochlear potential and paracellular permeability of a biotin-based tracer in the stria vascularis were unaltered. Freeze-fracture electron microscopy revealed disruption of the strands of intramembrane particles connecting bicellular and tricellular junctions in the inner ear epithelia of tricellulin-deficient mice. These ultrastructural changes may selectively affect the paracellular permeability of ions or small molecules, resulting in a toxic microenvironment for cochlear hair cells. Consistent with this hypothesis, hair cell loss was rescued in tricellulin-deficient mice when generation of normal endolymph was inhibited by a concomitant deletion of the transcription factor, Pou3f4. Finally, comprehensive phenotypic screening showed a broader pathological phenotype in the mutant mice, which highlights the non-redundant roles played by tricellulin.
Case-Crossover Analysis of Air Pollution Health Effects: A Systematic Review of Methodology and Application
Authors: Eduardo Carracedo-Martínez, Margarita Taracido, Aurelio Tobias, Marc Saez, Adolfo Figueiras
Journal: Environmental Health Perspectives (2010)

Case-crossover is one of the most used designs for analyzing the health-related effects of air pollution. Nevertheless, no one has reviewed its application and methodology in this context.We conducted a systematic review of case-crossover (CCO) designs used to study the relationship between air pollution and morbidity and mortality, from the standpoint of methodology and application.A search was made of the MEDLINE and EMBASE databases.Reports were classified as methodologic or applied. From the latter, the following information was extracted: author, study location, year, type of population (general or patients), dependent variable(s), independent variable(s), type of CCO design, and whether effect modification was analyzed for variables at the individual level.The review covered 105 reports that fulfilled the inclusion criteria. Of these, 24 addressed methodological aspects, and the remainder involved the design's application. In the methodological reports, the designs that yielded the best results in simulation were symmetric bidirectional CCO and time-stratified CCO. Furthermore, we observed an increase across time in the use of certain CCO designs, mainly symmetric bidirectional and time-stratified CCO. The dependent variables most frequently analyzed were those relating to hospital morbidity; the pollutants most often studied were those linked to particulate matter. Among the CCO-application reports, 13.6% studied effect modification for variables at the individual level.The use of CCO designs has undergone considerable growth; the most widely used designs were those that yielded better results in simulation studies: symmetric bidirectional and time-stratified CCO. However, the advantages of CCO as a method of analysis of variables at the individual level are put to little use.