tbuckley/cabot-search huggingface dataset:
Effect of Chest X-Rays on the Risk of Breast Cancer Among <i>BRCA1/2</i> Mutation Carriers in the International <i>BRCA1/2</i> Carrier Cohort Study: A Report from the EMBRACE, GENEPSO, GEO-HEBON, and IBCCS Collaborators’ Group
Authors: Nadine Andrieu, Douglas F. Easton, Jenny Chang-Claude, Matti A. Rookus, Richard Brohet, Elisabeth Cardis, Antonis C. Antoniou, Teresa Wagner, Jacques Simard, Gareth Evans, Susan Peock, Jean-Pierre Fricker, Catherine Nogues, Laura Van't Veer, Flora E. Van Leeuwen, David E. Goldgar
Journal: Journal of Clinical Oncology (2006)

Women who carry germline mutations in the BRCA1 and BRCA2 genes are at greatly increased risk of breast cancer (BC). Numerous studies have shown that moderate to high doses of ionizing radiation are a risk factor for BC. Because of the role of the BRCA proteins in DNA repair, we hypothesized that BRCA carriers might be more sensitive to ionizing radiation than women in the general population.A retrospective cohort study of 1,601 female BRCA1/2 carriers was performed. Risk of breast cancer from exposure to chest x-rays, as assessed by questionnaire data, was analyzed using a weighted Cox proportional hazards model.In this cohort, any reported exposure to chest x-rays was associated with an increased risk of BC (hazard ratio [HR] = 1.54; P = .007). This risk was increased in carrier women aged 40 years and younger (HR = 1.97; P < .001) and in women born after 1949 (HR = 2.56; P < .001), particularly those exposed only before the age of 20 years (HR = 4.64; P < .001).In our series of BRCA carriers, we detected a relatively large effect on BC risk with a level of radiation exposure that is at least an order of magnitude lower than in previously studied medical radiation-exposed cohorts. Although part of this increase may be attributable to recall bias, the observed patterns of risk in terms of age at exposure and attained age are consistent with those found in previous studies. If confirmed, the results have important implications for the use of x-ray imaging in young BRCA1/2 carriers.
RNA-Based Gene Therapy for HIV with Lentiviral Vector–Modified CD34 <sup>+</sup> Cells in Patients Undergoing Transplantation for AIDS-Related Lymphoma
Authors: David L. DiGiusto, Amrita Krishnan, Lijing Li, Haitang Li, Shirley Li, Anitha Rao, Shu Mi, Priscilla Yam, Sherri Stinson, Michael Kalos, Joseph Alvarnas, Simon F. Lacey, Jiing-Kuan Yee, Mingjie Li, Larry Couture, David Hsu, Stephen J. Forman, John J. Rossi, John A. Zaia
Journal: Science Translational Medicine (2010)

AIDS patients who develop lymphoma are often treated with transplanted hematopoietic progenitor cells. As a first step in developing a hematopoietic cell-based gene therapy treatment, four patients undergoing treatment with these transplanted cells were also given gene-modified peripheral blood-derived (CD34(+)) hematopoietic progenitor cells expressing three RNA-based anti-HIV moieties (tat/rev short hairpin RNA, TAR decoy, and CCR5 ribozyme). In vitro analysis of these gene-modified cells showed no differences in their hematopoietic potential compared with nontransduced cells. In vitro estimates of successful expression of the anti-HIV moieties were initially as high as 22% but declined to approximately 1% over 4 weeks of culture. Ethical study design required that patients be transplanted with both gene-modified and unmanipulated hematopoietic progenitor cells obtained from the patient by apheresis. Transfected cells were successfully engrafted in all four infused patients by day 11, and there were no unexpected infusion-related toxicities. Persistent vector expression in multiple cell lineages was observed at low levels for up to 24 months, as was expression of the introduced small interfering RNA and ribozyme. Therefore, we have demonstrated stable vector expression in human blood cells after transplantation of autologous gene-modified hematopoietic progenitor cells. These results support the development of an RNA-based cell therapy platform for HIV.
Genetic regulation of the antibody response to H-2Db alloantigens in mice. III. Inhibition of the IgG Response to noncongenic cells by preimmunization with congenic cells.
Authors: D Wernet, H Shafran, F Lilly
Journal: The Journal of Experimental Medicine (1976)

When B10.A (5R) mice (H-12i5) are immunized with spleen cells from congenic B10 mice (H-12b), they respond to alloantigens of the H-2Db region by producing antibodies of only IgM type. In contrast, they produce both IgM and IgG antibodies when immunized with A.BY cells (H-2b) that carry other foreign cell surface antigens (non-H-2) in addition to H-2Db. Preimmunization of 5R mice with two injections of congenic cells leads to an H-2Db specific inhibition of the IgG response to a subsequent immunization with A.BY cells. It is concluded that congenic B10 cells fail to activate helper T cells which are necessary to induce the switch from IgM to IgG production. Instead T- or B-cell tolerance may be induced with prohibits the subsequent IgG response to A.BY cells, possibly by way of suppressor T cells which may act either on B cells directly or via helper T cells.
Mammary Tumorigenesis in Chemical Carcinogen-Treated Mice. I. Incidence in BALB/c and C57BL Mice2
Authors: Daniel Medina
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Mammary Tumorigenesis in Chemical Carcinogen-Treated Mice. I. Incidence in BALB/c and C57BL Mice Get access Daniel Medina Daniel Medina 3Department of Cell Biology, Baylor College of Medicine, Houston, Tex. 77025. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 1, July 1974, Pages 213–221, https://doi.org/10.1093/jnci/53.1.213 Published: 01 July 1974 Article history Received: 11 January 1974 Accepted: 10 April 1974 Published: 01 July 1974
Effects of aging on the work output and efficiency of rat papillary muscle
Authors: H Kiriazis, C L Gibbs
Journal: Cardiovascular Research (2000)

This study aimed to investigate the effect of aging on the work output and efficiency of rat papillary muscle.The mechanical and energetic properties of left ventricular papillary muscle preparations isolated from 6-, 15-, and 27- to 32-month-old Sprague-Dawley rats were measured in myothermic experiments at 27 degrees C at a stimulus frequency of 0.167 Hz.We found that the basal metabolism measured in quiescent papillary muscles was significantly reduced in the 27- to 32-month-old group (4.9 mWg(-1) compared to 7.7 and 7.0 mWg(-1) in the 6- and 15-month groups). In isotonic experiments, the work output (at a range of afterloads) was significantly depressed for the 27- to 32-month group being only 52% of the work output of the 6-month group. This outcome was due to a decrease in both the extent of muscle shortening only, 66% of 6- and 15-month data, and in the maximum force developed. The reduced work was accompanied by a parallel decrease in energy consumption (enthalpy) and hence, the net mechanical efficiency (work/active enthalpyx100%) was not altered. A force-length- area (FLA) analysis was applied to the isotonic data and an energy: FLA regression line was obtained for each preparation. We found that there were no significant differences in either the intercept or slope of the energy: FLA relation with age. Contractile efficiency (39+/-3%) in the 27- to 32-month group was not significantly different to that found in the 6-month (43+/-4%) or 15-month (40+/-3% group).There are no changes in the mechanical performance or efficiency of cardiac muscle from young (6-month-old) or adult (15-month-old) rats but in the aged and senescent rats (27-32-month-old) there is a pronounced decline in stress development and shortening ability leading to a fall in work output. Mechanical and contractile efficiency however remain unchanged in old age and the data resembles that obtained in pressure overload hypertrophy.
Forkhead box p3+ regulatory T cell underlies male resistance to experimental type 2 autoimmune hepatitis
Authors: Pascal Lapierre, Kathie Béland, Caroline Martin, Fernando Alvarez, Fernando Alvarez
Journal: Hepatology (2010)

Autoimmune hepatitis (AIH), like many autoimmune diseases, is most prevalent in young women. The immunological basis of this age and sex susceptibility bias was investigated in a murine model of AIH. Xenoimmunization of 7-week-old female C57BL/6 mice resulted in more severe AIH with higher levels of liver inflammation, serum alanine aminotransferase, specific T-cell cytotoxicity, and autoantibody than younger and older females. Vaccinated males developed minimal liver inflammation and higher percentages of CD4+CD25+FoxP3+ regulatory T cell in peripheral blood mononuclear cells, spleen, and liver than females. Regulatory T cells (Tregs) were virtually absent in liver-lymphocytes infiltrates of females. Castration of C57BL/6 mice, with or without 17β-estradiol supplementation, did not modify susceptibility in males, nor Treg numbers, suggesting minimal contribution of testosterone and estradiol to autoimmune hepatitis (AIH) susceptibility. Xenoimmunized Aire (+/0) mouse displayed similar AIH susceptibility, sex bias, and Tregs numbers as C57BL/6 mice, suggesting that susceptibility in females is not the result of less stringent thymic central tolerance. Autoreactive B cell response against formiminotransferase-cyclodeaminase correlated with disease activity, possibly linking B-cell autoreactivity and AIH pathogenesis. Conclusion : Peripheral tolerance and development of regulatory T cells after self-mimicking antigen exposure, and not sexual hormone nor central tolerance, are the main factors for susceptibility to AIH in females. Hepatology 2010
The Cost-Effectiveness of Cyclooxygenase-2 Selective Inhibitors in the Management of Chronic Arthritis
Authors: Brennan M.R. Spiegel, Laura Targownik, Gareth S. Dulai, Ian M. Gralnek
Journal: Annals of Internal Medicine (2003)

Background: Rofecoxib and celecoxib (coxibs) effectively treat chronic arthritis pain and reduce ulcer complications by 50% compared with nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). However, their absolute risk reduction is small and the cost-effectiveness of treatment is uncertain. Objective: To determine whether the degree of risk reduction in gastrointestinal complications by coxibs offsets their increased cost compared with a generic nonselective NSAID. Design: Cost-utility analysis. Data Sources: Systematic review of MEDLINE and published abstracts. Target Population: Patients with osteoarthritis or rheumatoid arthritis who are not taking aspirin and who require long-term NSAID therapy for moderate to severe arthritis pain. Perspective: Third-party payer. Interventions: Naproxen, 500 mg twice daily, and coxib, once daily. Patients intolerant of naproxen were switched to a coxib. Time Horizon: Lifetime. Outcome Measures: Incremental cost per quality-adjusted life-year (QALY) gained. Results of Base-Case Analysis: Using a coxib instead of a nonselective NSAID in average-risk patients cost an incremental $275 809 per year to gain 1 additional QALY. Results of Sensitivity Analysis: The incremental cost per QALY gained decreased to $55 803 when the analysis was limited to the subset of patients with a history of bleeding ulcers. The coxib strategy became dominant when the cost of coxibs was reduced by 90% of the current average wholesale price. In probabilistic sensitivity analysis, if a third-party payer was willing to pay $150 000 per QALY gained, then 4.3% of average-risk patients would fall within the budget. Conclusions: The risk reduction seen with coxibs does not offset their increased costs compared with nonselective NSAIDs in the management of average-risk patients with chronic arthritis. However, coxibs may provide an acceptable incremental cost-effectiveness ratio in the subgroup of patients with a history of bleeding ulcers.
Intrathymic and extrathymic development of human plasmacytoid dendritic cell precursors in vivo
Authors: Kees Weijer, Christel H. Uittenbogaart, Arie Voordouw, Franka Couwenberg, Jurgen Seppen, Bianca Blom, Florry A. Vyth-Dreese, Hergen Spits
Journal: Blood (2002)
Duration of the antihistaminic effect after discontinuation of ebastine
Authors: N. Frossard, D. Vital‐Durand, N. Mounedji, A. Valleteau
Journal: Allergy (2001)

Background: The inhibitory effect of antihistamines on allergen‐induced skin reactions can impair the results of allergen skin testing, which are necessary for the diagnosis of atopic diseases. This study was designed to determine the time period required for the inhibitory effect of ebastine on allergen‐induced skin reactivity to disappear completely. Methods: This was a double‐blind, placebo‐controlled, parallel‐group study including 23 out of 27 randomized patients. They received either ebastine 20 mg or placebo once daily for 7 days. At the end of treatment, allergen challenge was performed daily for 7 days. Histamine challenge was performed on day 1 (6 and 24 h) and day 5 after treatment. The wheal and flare surface areas were measured and analyzed. Results: Highly significant inhibition of the wheal and flare response induced by allergen was observed after ebastine treatment on days 1 and 2 as compared with placebo ( P &lt;0.01 for both). The inhibition was reduced, although still significant, by day 3 ( P &lt;0.05). No significant difference was observed by day 4 between the ebastine and the placebo groups. The effects of histamine challenge were significantly reduced in the ebastine compared with the placebo group at day 1 (6 and 24 h), and were similar at day 5 after treatment. Conclusions: Our results show that the wheal and flare response to allergen after ebastine discontinuation returns to placebo values after 4 days. Therefore, patients using ebastine need to be antihistamine‐free for 4 days before the skin prick test. This is valuable information for the allergologist seeking to diagnose allergen sensitivity.
Regulation of Transforming Growth Factor-β1–Induced Apoptosis and Epithelial-to-Mesenchymal Transition by Protein Kinase A and Signal Transducers and Activators of Transcription 3
Authors: Yanan Yang, Xinchao Pan, Weiwei Lei, Jun Wang, Jian Shi, Fuqiang Li, Jianguo Song
Journal: Cancer Research (2006)

Abstract Apoptosis and epithelial-to-mesenchymal transdifferentiation or transition (EMT) are crucial for normal development and body homeostasis. The alterations of these events are closely related to some pathologic processes, such as tumor formation and metastasis, fibrotic diseases of liver and kidney, and abnormal development of embryos. The mechanism that underlies the simultaneously occurring apoptosis and EMT induced by transforming growth factor-β (TGF-β) has not been well studied. In this report, we investigated the potential mechanism that underlies TGF-β1–induced apoptosis and EMT. TGF-β1–induced apoptosis and EMT were associated with the activation of protein kinase A (PKA) and signal transducers and activators of transcription 3 (STAT3). Inhibition of PKA by specific PKA inhibitor H89 or by PKA inhibitor peptide blocked STAT3 activation and suppressed TGF-β1–induced apoptosis and EMT. Furthermore, overexpression of a phosphorylation-deficient form of STAT3, but not wild-type STAT3, produced an inhibitory effect on TGF-β1–induced apoptosis and EMT. The results indicate that PKA is an upstream regulator for TGF-β1–induced STAT3 activation and plays an important role in TGF-β1–mediated apoptosis and EMT. These studies provided a new insight into the signaling mechanism underlying the apoptosis and EMT, which could be of importance in understanding some related physiologic and pathologic processes. (Cancer Res 2006; 66(17): 8617-24)
Allergic and irritant contact dermatitis compared in the treatment of alopecia totalis and universalis. A comparison of the value of topical diphencyprone and tretinoin gel
Authors: J. ASHWORTH, E. TUYP, RONA M. MACKIE
Journal: British Journal of Dermatology (1989)

Journal Article Allergic and irritant contact dermatitis compared in the treatment of alopecia totalis and universalis. A comparison of the value of topical diphencyprone and tretinoin gel Get access J. ASHWORTH, J. ASHWORTH University Department of Dermatology, Western Infirmary, Glasgow GII 6NT, U.K. Dr J. Ashworth, Department of Dermatology, Charing Cross Hospital, Fulham Palace Road, London W6 8RF, U.K. Search for other works by this author on: Oxford Academic Google Scholar E. TUYP, E. TUYP University Department of Dermatology, Western Infirmary, Glasgow GII 6NT, U.K. Search for other works by this author on: Oxford Academic Google Scholar RONA M. MACKIE RONA M. MACKIE University Department of Dermatology, Western Infirmary, Glasgow GII 6NT, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 120, Issue 3, 1 March 1989, Pages 397–401, https://doi.org/10.1111/j.1365-2133.1989.tb04166.x Published: 01 March 1989
Phase II Study of High-Dose [<sup>131</sup>I]Metaiodobenzylguanidine Therapy for Patients With Metastatic Pheochromocytoma and Paraganglioma
Authors: Sara Gonias, Robert Goldsby, Katherine K. Matthay, Randall Hawkins, David Price, John Huberty, Lloyd Damon, Charles Linker, Aimee Sznewajs, Steve Shiboski, Paul Fitzgerald
Journal: Journal of Clinical Oncology (2009)

To evaluate the safety and efficacy of high-dose [(131)I]metaiodobenzylguanidine ([(131)I]MIBG) in the treatment of malignant pheochromocytoma (PHEO) and paraganglioma (PGL).Fifty patients with metastatic PHEO or PGL, age 10 to 64 years, were treated with [(131)I]MIBG doses ranging from 492 to 1,160 mCi (median, 12 mCi/kg). Cumulative [(131)I]MIBG administered ranged from 492 to 3,191 mCi. Autologous hematopoietic stem cells were collected and cryopreserved before treatment with [(131)I]MIBG greater than 12 mCi/kg or with a total dose greater than 500 mCi. Sixty-nine [(131)I]MIBG infusions were given, which included infusions to 35 patients treated once and infusions to 15 patients who received two or three treatments. Response was evaluated by [(123)I]MIBG scans, computed tomography/magnetic resonance imaging, urinary catecholamines/metanephrines, and chromogranin A.The overall complete response (CR) plus partial response (PR) rate in 49 evaluable patients was 22%. Additionally, 35% of patients achieved a CR or PR in at least one measure of response without progressive disease, and 8% of patients maintained stable disease for greater than 12 months. Thirty-five percent of patients experienced progressive disease within 1 year after therapy. The estimated 5-year overall survival rate was 64%. Toxicities included grades 3 to 4 neutropenia (87%) and thrombocytopenia (83%). Grades 3 to 4 nonhematologic toxicity included acute respiratory distress syndrome (n = 2), bronchiolitis obliterans organizing pneumonia (n = 2), pulmonary embolism (n = 1), fever with neutropenia (n = 7), acute hypertension (n = 10), infection (n = 2), myelodysplastic syndrome (n = 2), and hypogonadism (n = 4).Although serious toxicity may occur, the survival and response rates achieved with high-dose [(131)I]MIBG suggest its utility in the management of selected patients with metastatic PHEO and PGL.
Circadian Variation in the Efficacy of Tissue-Type Plasminogen Activator
Authors: Peter B. Kurnik
Journal: Circulation (1995)

Background The frequency of onset of acute myocardial infarction follows a circadian pattern, with a peak incidence between 6:00 am and noon. Circadian variations have been defined for platelet aggregation, plasminogen-activator inhibitor, and a number of hemostatic and physiological factors, all of which might predispose toward clotting in the late morning and thrombolysis in the evening. Thus, the hypothesis for this retrospective analysis was that tissue-type plasminogen activator (TPA) has greater efficacy when administered between noon and midnight, as measured by coronary patency 90 minutes after initiation of treatment. Methods and Results Seven hundred twenty-eight patients were enrolled in either of two studies in which TPA was administered under a uniform protocol for the treatment of acute myocardial infarction. Of these, 692 patients had qualifying arteriograms that allowed standardized assessment by a core angiographic laboratory of the primary end point of 90-minute patency. TPA has a circadian pattern of efficacy, with greater TIMI grade 3 patency when administered between noon and midnight ( P &lt;.001). When TPA was given within 2 hours of symptoms (n=127), the total patency was highest and there was a trend ( P =.055) toward the greatest magnitude difference occurring between am and pm patency. The onset of myocardial infarction was confirmed to have a marked circadian variation with a peak incidence about 10:00 am . The peak efficacy of TPA was about 8:00 pm , representing a phase difference of about 10 hours after peak infarction incidence. Conclusions There is a circadian variation in the ability of TPA to rapidly open coronary arteries, with highest efficacy between noon and midnight. This complements clinical and in vitro knowledge of increased morning thrombosis and is concordant with knowledge of a fibrinolytic profile that is more favorable for evening lysis. This finding has implications for understanding the circadian pathophysiology of myocardial infarction and for its chronotherapy.
Nontuberculous Mycobacteria
Authors: Kenneth N. Olivier, David J. Weber, Richard J. Wallace, Ali R. Faiz, Ji-Hyun Lee, Yansheng Zhang, Barbara A. Brown-Elliot, Allison Handler, Rebecca W. Wilson, Michael S. Schechter, Lloyd J. Edwards, Subha Chakraborti, Michael R. Knowles
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Nontuberculous mycobacteria (NTM) are potential respiratory pathogens in cystic fibrosis (CF). To assess the species-specific prevalence and risk factors for acquisition, we conducted a prospective, cross-sectional study of the prevalence of NTM and clinical features of patients at 21 U.S. centers. Almost 10% of patients with CF who were 10 years or older were included (n = 986). The overall prevalence of NTM in sputum was 13.0% (range by center, 7-24%). Mycobacterium avium complex (72%) and Mycobacterium abscessus (16%) were the most common species. When compared with patients with CF without NTM, culture-positive subjects were older (26 vs. 22 years, p < 0.001), had a higher FEV1 (60 vs. 54%, p < 0.01), higher frequency of Staphylococcus aureus (43 vs. 31%, p < 0.01), and lower frequency of Pseudomonas aeruginosa (71 vs. 82%, p < 0.01). Molecular typing revealed that almost all patients within each center had unique NTM strains. In summary, NTM are common in patients with CF, but neither person-to-person nor nosocomial acquisition explained the high prevalence. Older age was the most significant predictor for isolation of NTM. The clinical significance of NTM in CF is incompletely defined, but patients with these organisms should be monitored with repeat cultures.