tbuckley/cabot-search huggingface dataset:
Risedronate Prevents Bone Loss in Breast Cancer Survivors: A 2-Year, Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Authors: Susan L. Greenspan, Adam Brufsky, Barry C. Lembersky, Rajib Bhattacharya, Karen T. Vujevich, Subashan Perera, Susan M. Sereika, Victor G. Vogel
Journal: Journal of Clinical Oncology (2008)

Limited data are available on the efficacy of oral bisphosphonate therapy in breast cancer survivors. Our goal was to examine prevention of breast cancer-related bone loss in this cohort.Eighty-seven postmenopausal women after chemotherapy for breast cancer were randomly assigned to once-weekly risedronate 35 mg or placebo for 24 months. Outcomes included bone mineral density (BMD) and turnover markers.At study initiation, 13% of patients were on an aromatase inhibitor (AI). After 24 months, there were differences of 1.6 to 2.5% (P < .05) at the spine and hip BMD between the placebo and risedronate groups. At study completion, 44% were on an AI. Adjusting for an AI, women on placebo plus AI had a decrease in BMD of (mean +/- SE) 4.8% +/- 0.8% at the spine and 2.8% +/- 0.5% at the total hip (both P < .001). In women on risedronate + AI, the spine decreased by 2.4% +/- 1.1% (P < .05) and was stable at the hip. Women in the placebo group not on an AI, maintained BMD at the spine, and had a 1.2% +/- 0.5% loss at the total hip (P < .05). Women who received risedronate but no AI had the greatest improvement in BMD of 2.2% +/- 0.9% (P < .05) at the total hip. Bone turnover was reduced with risedronate. There were no differences in adverse events between the groups.We conclude that in postmenopausal women with breast cancer with or without AI therapy, once-weekly oral risedronate was beneficial for spine and hip BMD, reduced bone turnover, and was well tolerated.
GLUCAGON ANTIBODIES AND AN IMMUNOASSAY FOR GLUCAGON*
Authors: Roger H. Unger, Anna M. Eisentraut, M. S. McCall, Leonard L. Madison
Journal: Journal of Clinical Investigation (1961)

Despite extensive knowledge of the amino acid composition of beef-pork glucagon, and of the physiologic changes induced by its administration to animals and man, the role of glucagon in the homeostatic regulation of blood glucose level in normal and abnormal states remains to be defined.This fundamental gap in knowledge is the result of the lack of a method sufficiently specific and sensitive to measure endogenous glucagon in body fluids.Previous efforts to assay glucagon in plasma have been based upon ability to produce either hyperglycemia in a living animal (1-3), glycogenolysis in liver slices (4), or phosphorylase activation in liver homogenates (5).There is reason to doubt the specificity of the plasma glucagon-like activity detectable by such methods (6), and their status is at present in question.The greater specificity inherent in immunoas- says (7), coupled with the unprecedented sensi- tivity provided by the paper radiochromato-elec- trophoretic techniques of Berson and co-workers (8) suggested that a radio-immunoassay for glu- cagon might provide a hitherto unequaled range of specific measurements.In a preliminary report, the antigenicity of beef-pork glucagon in rabbits was recorded and the feasibility of a radioimmunoassay for glucagon demonstrated (9).The development by Berson and Yalow of a ra- dio-immunoassay for insulin of remarkable sensi- tivity and specificity (10, 11) has validated this approach to problems of peptide hormone assay.In the following report the antigenicity of glucagon is demonstrated, glucagon antibodies are
Gain of MYC underlies recurrent trisomy of the MYC chromosome in acute promyelocytic leukemia
Authors: Letetia Jones, Guangwei Wei, Sabina Sevcikova, Vernon Phan, Sachi Jain, Angell Shieh, Jasmine C. Y. Wong, Min Li, Joshua Dubansky, Mei Lin Maunakea, Rachel Ochoa, George Zhu, Thelma R. Tennant, Kevin M. Shannon, Scott W. Lowe, Michelle M. Le Beau, Scott C. Kogan
Journal: The Journal of Experimental Medicine (2010)

Gain of chromosome 8 is the most common chromosomal gain in human acute myeloid leukemia (AML). It has been hypothesized that gain of the MYC protooncogene is of central importance in trisomy 8, but the experimental data to support this are limited and controversial. In a mouse model of promyelocytic leukemia in which the MRP8 promoter drives expression of the PML-RARA fusion gene in myeloid cells, a Myc allele is gained in approximately two-thirds of cases as a result of trisomy for mouse chromosome 15. We used this model to test the idea that MYC underlies acquisition of trisomy in AML. We used a retroviral vector to drive expression of wild-type, hypermorphic, or hypomorphic MYC in bone marrow that expressed the PML-RARA transgene. MYC retroviruses cooperated in myeloid leukemogenesis and suppressed gain of chromosome 15. When the PML-RARA transgene was expressed in a Myc haploinsufficient background, we observed selection for increased copies of the wild-type Myc allele concomitant with leukemic transformation. In addition, we found that human myeloid leukemias with trisomy 8 have increased MYC. These data show that gain of MYC can contribute to the pathogenic effect of the most common trisomy of human AML.
PD-1 and Its Ligands in Tolerance and Immunity
Authors: Mary E. Keir, Manish J. Butte, Gordon J. Freeman, Arlene H. Sharpe
Journal: Annual Review of Immunology (2008)

Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, deliver inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. Immune responses to foreign and self-antigens require specific and balanced responses to clear pathogens and tumors and yet maintain tolerance. Induction and maintenance of T cell tolerance requires PD-1, and its ligand PD-L1 on nonhematopoietic cells can limit effector T cell responses and protect tissues from immune-mediated tissue damage. The PD-1:PD-L pathway also has been usurped by microorganisms and tumors to attenuate antimicrobial or tumor immunity and facilitate chronic infection and tumor survival. The identification of B7-1 as an additional binding partner for PD-L1, together with the discovery of an inhibitory bidirectional interaction between PD-L1 and B7-1, reveals new ways the B7:CD28 family regulates T cell activation and tolerance. In this review, we discuss current understanding of the immunoregulatory functions of PD-1 and its ligands and their therapeutic potential.
A cluster randomised controlled trial evaluating the effectiveness of a structured pulmonary rehabilitation education programme in a primary care setting for people with chronic obstructive pulmonary disease (COPD): The PRINCE study
Authors: Dympna Casey, Kathy Murphy, Devane Declan, Adeline Cooney, Bernard McCarthy, Lorraine Mee, John Newell, Carl Scarrott, Eamon O Shea, Collette Kirwan, Paddy Gillespie, Andrew W. Murphy
Journal: European Respiratory Journal (2013)

Little is known about the impact of structured education pulmonary rehabilitation programmes (SEPRP’s) delivered in primary care. Objective: To evaluate the effectiveness of a SEPRP based in primary care, on the health status of people with COPD. Design: A two-arm, cluster RCT, with randomization at practice level. 32 primary care centers in Ireland. 178 participants with COPD were randomized to the intervention and 172 to control. Experimental group received SEPRP, delivered by a practice nurse and a physiotherapist, 2 hours per week over 8 weeks. Control group received usual care. Health status, measured by the CRQ at baseline and at 12-14 weeks was the primary outcome measure.Outcomes assessments were blinded to group allocation. 143 of 178 (52%) patients in the intervention and 134 of 172 (48%) in control completed post intervention assessments. Participants allocated to the intervention had statistically significant higher mean change total CRQ scores (adjusted mean difference (MD) 1.11, 95% CI 0•35 to 1.87). They also had statistically significant higher mean CRQ Dyspnoea scores after intervention (adjusted MD 0•49, 95% CI 0•20 to 0.78) and CRQ Physical scores (adjusted MD 0•37, 95% CI 0•14 to 0.60). However, CI’s for total CRQ score, CRQ Dyspnoea and CRQ Physical subscales do not exclude smaller differences pre-specified as clinically important. The NNT for the Total CRQ was 7. No other statistically significant differences were seen. A SEPRP based in primary care is feasible and may increase local accessibility to people with COPD.
Particulate Air Pollution, Oxidative Stress Genes, and Heart Rate Variability in an Elderly Cohort
Authors: Teresa Chahine, Andrea Baccarelli, Augusto Litonjua, Robert O. Wright, Helen Suh, Diane R. Gold, David Sparrow, Pantel Vokonas, Joel Schwartz
Journal: Environmental Health Perspectives (2007)

We have previously shown that reduced defenses against oxidative stress due to glutathione S-transferase M1 (GSTM1) deletion modify the effects of PM(2.5) (fine-particulate air pollution of < 2.5 microm in aerodynamic diameter) on heart rate variability (HRV) in a cross-sectional analysis of the Normative Aging Study, an elderly cohort. We have extended this to include a longitudinal analysis with more subjects and examination of the GT short tandem repeat polymorphism in the heme oxygenase-1 (HMOX-1) promoter.HRV measurements were taken on 539 subjects. Linear mixed effects models were fit for the logarithm of HRV metrics-including standard deviation of normal-to-normal intervals (SDNN), high frequency (HF), and low frequency (LF)-and PM(2.5) concentrations in the 48 hr preceding HRV measurement, controlling for confounders and a random subject effect.PM(2.5) was significantly associated with SDNN (p = 0.04) and HF (p = 0.03) in all subjects. There was no association in subjects with GSTM1, whereas there was a significant association with SDNN, HF, and LF in subjects with the deletion. Similarly, there was no association with any HRV measure in subjects with the short repeat variant of HMOX-1, and significant associations in subjects with any long repeat. We found a significant three-way interaction of PM(2.5) with GSTM1 and HMOX-1 determining SDNN (p = 0.008), HF (p = 0.01) and LF (p = 0.04). In subjects with the GSTM1 deletion and the HMOX-1 long repeat, SDNN decreased by 13% [95% confidence interval (CI), -21% to -4%], HF decreased by 28% (95% CI, -43% to -9%), and LF decreased by 20% (95% CI, -35% to -3%) per 10 microg/m(3) increase in PM.Oxidative stress is an important pathway for the autonomic effects of particles.
Colorectal Cancer Risks in Relatives of Young-Onset Cases: Is Risk the Same Across All First-Degree Relatives?
Authors: Lisa A. Boardman, Bruce W. Morlan, Kari G. Rabe, Gloria M. Petersen, Noralane M. Lindor, Sandra K. Nigon, Julia Goldberg, Steven Gallinger
Journal: Clinical Gastroenterology and Hepatology (2007)
Nuclear export regulation of COP1 by 14-3-3σ in response to DNA damage
Authors: Chun-Hui Su, Ruiying Zhao, Guermarie Velazquez-Torres, Jian Chen, Christopher Gully, Sai-Ching J Yeung, Mong-Hong Lee
Journal: Molecular Cancer (2010)

Mammalian constitutive photomorphogenic 1 (COP1) is a p53 E3 ubiquitin ligase involved in regulating p53 protein level. In plants, the dynamic cytoplasm/nucleus distribution of COP1 is important for its function in terms of catalyzing the degradation of target proteins. In mammalian cells, the biological consequence of cytoplasmic distribution of COP1 is not well characterized. Here, we show that DNA damage leads to the redistribution of COP1 to the cytoplasm and that 14-3-3σ, a p53 target gene product, controls COP1 subcellular localization. Investigation of the underlying mechanism suggests that COP1 S387 phosphorylation is required for COP1 to bind 14-3-3σ. Significantly, upon DNA damage, 14-3-3σ binds to phosphorylated COP1 at S387, resulting in COP1's accumulation in the cytoplasm. Cytoplasmic COP1 localization leads to its enhanced ubiquitination. We also show that N-terminal 14-3-3σ interacts with COP1 and promotes COP1 nuclear export through its NES sequence. Further, we show that COP1 is important in causing p53 nuclear exclusion. Finally, we demonstrate that 14-3-3σ targets COP1 for nuclear export, thereby preventing COP1-mediated p53 nuclear export. Together, these results define a novel, detailed mechanism for the subcellular localization and regulation of COP1 after DNA damage and provide a mechanistic explanation for the notion that 14-3-3σ's impact on the inhibition of p53 E3 ligases is an important step for p53 stabilization after DNA damage.
High-Throughput Tyrosine Kinase Activity Profiling Identifies FAK as a Candidate Therapeutic Target in Ewing Sarcoma
Authors: Brian D. Crompton, Anne L. Carlton, Aaron R. Thorner, Amanda L. Christie, Jinyan Du, Monica L. Calicchio, Miguel N. Rivera, Mark D. Fleming, Nancy E. Kohl, Andrew L. Kung, Kimberly Stegmaier
Journal: Cancer Research (2013)

Limited progress has been made in the treatment of advanced-stage pediatric solid tumors despite the accelerated pace of cancer discovery over the last decade. Tyrosine kinase inhibition is one tractable therapeutic modality for treating human malignancy. However, little is known about the kinases critical to the development or maintenance of many pediatric solid tumors such as Ewing sarcoma. Using a fluorescent, bead-based technology to profile activated tyrosine kinases, we identified focal adhesion kinase (FAK, PTK2) as a candidate target in Ewing sarcoma. FAK is a tyrosine kinase critical for cellular adhesion, growth, and survival. As such, it is a compelling target for cancer-based therapy. In this study, we have shown that FAK is highly phosphorylated in primary Ewing sarcoma tumor samples and that downregulation of FAK by short hairpin RNA and treatment with a FAK-selective kinase inhibitor, PF-562271, impaired growth and colony formation in Ewing sarcoma cell lines. Moreover, treatment of Ewing sarcoma cell lines with PF-562271 induced apoptosis and led to downregulation of AKT/mTOR and CAS activity. Finally, we showed that small-molecule inhibition of FAK attenuated Ewing sarcoma tumor growth in vivo. With FAK inhibitors currently in early-phase clinical trials for adult malignancies, these findings may bear immediate relevance to patients with Ewing sarcoma.
Genetic aspects of susceptibility to air pollution
Authors: S.R. Kleeberger
Journal: European Respiratory Journal (2003)

Inter-individual variation in human responses to air pollutants suggests that some subpopulations are at increased risk, and it is increasingly clear that genetic background is an important susceptibility factor. Genetically standardised animal models provide useful investigative tools. Linkage analyses using inbred mice identified chromosomal segments (quantitative trait loci (QTL)), with genes controlling susceptibility to the lung inflammatory (chromosome 17), injury (chromosome 11), and hyperpermeability (chromosome 4) responses to ozone (O3) exposure. An immune dysfunction response induced by exposure to sulphate-associated particles is linked to the identical chromosome 17 and 11 QTLs described for O3 susceptibility, thus similar genetic mechanisms may be controlling pulmonary responses to these pollutants. Candidate genes within the QTLs on chromosomes 4 and 17 include the toll-like receptor 4 and the pro-inflammatory cytokine, tumour necrosis factor-alpha, respectively. Functional analyses strongly support a role for these candidate genes in determining susceptibility to O3 and particulates. Because striking linkage homology exists between the human and mouse genomes, candidate susceptibility genes identified in the mouse are likely to aid research aimed at understanding human genetic factors that contribute to differential susceptibility. To date, no studies have examined the interaction between age and genetic background in the development of air pollution-induced lung disease. However, investigations have suggested an influence of age on genetic susceptibility to lung cancer and other diseases, which indicate that an interaction between age and genetic background may be important in air pollution disease pathogenesis.
The Immunofluorescent "Band" Test for Lupus Erythematosus
Authors: Thomas K. Burnham, Gerald Fine
Journal: British Journal of Dermatology (1971)

Journal Article The Immunofluorescent “Band” Test for Lupus Erythematosus Get access Thomas K. Burnham, Thomas K. Burnham Henry Ford Hospital Detroit, Michigan 48202 Search for other works by this author on: Oxford Academic Google Scholar Gerald Fine Gerald Fine Henry Ford Hospital Detroit, Michigan 48202 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 84, Issue 2, 1 February 1971, Pages 176–177, https://doi.org/10.1111/j.1365-2133.1971.tb06864.x Published: 01 February 1971
Phase II Trial of Bortezomib for Patients With Advanced Renal Cell Carcinoma
Authors: G. Varuni Kondagunta, Beverly Drucker, Lawrence Schwartz, Jennifer Bacik, Stephanie Marion, Paul Russo, Madhu Mazumdar, Robert J. Motzer
Journal: Journal of Clinical Oncology (2004)

Purpose To assess the efficacy and toxicity of bortezomib (Velcade; Milennium Pharmaceuticals Inc, Cambridge, MA; formerly PS-341) in patients with metastatic renal cell carcinoma (RCC). Patients and Methods Thirty-seven patients with metastatic RCC were treated with bortezomib. The first 25 patients enrolled onto the trial were treated with a dose of 1.5 mg/m 2 . The dose was decreased to 1.3 mg/m 2 for the subsequent 12 patients, because more than 50% of the patients treated at the higher dose required dose reductions. Bortezomib was given by intravenous administration on a twice-weekly schedule for 2 weeks followed by 1 week without treatment until progression or unacceptable toxicity occurred. Twenty-three patients (62%) previously had undergone nephrectomy, and 19 patients (51%) had previously been treated with cytokine therapy. Results Of the 37 assessable patients, the best response was a partial response in four patients (11%; 95% CI, 3% to 25%) and stable disease in 14 patients (38%; 95% CI, 23% to 55%). The four patients with partial response experienced response durations of 8, 8+, 15+, and 20+ months. Grade 2 or 3 sensory neuropathy was present in 10 patients (53%) overall. One patient in the 1.5 mg/m 2 group had grade 3 sensory neuropathy; no grade 3 sensory neuropathy was seen in the 1.3 mg/m 2 group. Conclusion The results of this trial suggest that bortezomib has an antitumor effect in individual patients with metastatic RCC. The small proportion of patients who achieved a partial response does not support routine use in metastatic RCC. Efforts to identify the molecular profile associated with clinical response or combination therapy with interferon alfa or other novel agents, may be considered.
Mutation of JAK2 in the myeloproliferative disorders: timing, clonality studies, cytogenetic associations, and role in leukemic transformation
Authors: P. J. Campbell, E. J. Baxter, P. A. Beer, L. M. Scott, A. J. Bench, B. J. P. Huntly, W. N. Erber, R. Kusec, T. S. Larsen, S. Giraudier, M.-C. Le Bousse-Kerdiles, M. Griesshammer, J. T. Reilly, B. Y. Cheung, C. N. Harrison, A. R. Green
Journal: Blood (2006)
Prevalence of rheumatoid arthritis in Italy: the Chiavari study
Authors: M. A Cimmino, M. Parisi, G. Moggiana, G. S Mela, S. Accardo
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> To ascertain the prevalence of rheumatoid arthritis (RA) in an Italian general population. <h3>METHODS</h3> The study was performed in the years 1991–92 in Chiavari, a small town located on the Ligurian coast, and involved 4456 subjects aged 16 years or more from four general practices. The subjects received a postal questionnaire developed to detect patients with current or past inflammatory joint diseases. The age and sex distribution of the sample were similar to those of the Italian population from the 1992 census. Patients reporting a history of joint swelling in at least a pair of symmetrical joints were reviewed by a rheumatologist. The clinical records of non-responders and responders who failed to attend the clinic were also reviewed. <h3>RESULTS</h3> 3294 of 4456 (73.9%) subjects answered to the questionnaire. The mean (SD) age of the 3294 responders was 48.3 (19.3) years; 53.7% of them were female. Swelling in at least two symmetrical joints was reported by 230 subjects (7%). Among them, 11 patients fulfilling the 1987 ARA criteria for RA were identified. The prevalence of RA was 0.33% (95% CI 0.13, 0.53) in the general population, 0.13% (95% CI 0, 0.31) in men, and 0.51% (95% CI 0.18, 0.84) in women. <h3>CONCLUSIONS</h3> These data are consistent with the results of three earlier studies published in the fifties in the Italian literature and confirm that the prevalence of RA is low in Italy and has remained unchanged in the last 40 years.
Gene Expression and In Situ Localization of Diacylglycerol Kinase Isozymes in Normal and Infarcted Rat Hearts
Authors: Morihiko Takeda, Yutaka Kagaya, Jun Takahashi, Tadashi Sugie, Jun Ohta, Jun Watanabe, Kunio Shirato, Hisatake Kondo, Kaoru Goto
Journal: Circulation Research (2001)

Diacylglycerol (DG) kinase (DGK) terminates signaling from DG, which serves as an activator of protein kinase C (PKC), by converting DG to phosphatidic acid. DGK is thus regarded as an attenuator of the PKC activity. In rats, five DGK isozymes have been cloned, but little is known about their role in the heart. In this study, the spatiotemporal expression of DGK isozymes was investigated in rat hearts under a normal condition and after myocardial infarction (MI) by in situ hybridization histochemistry and immunohistochemistry. In normal left ventricular myocardium, DGKalpha, DGKepsilon, and DGKzeta mRNAs were expressed evenly throughout the myocardium, although the DGKalpha expression was very low. In infarcted hearts, the expression of DGKzeta was enhanced in the peripheral zone of the necrotic area and at the border zone 3 and 7 days after MI, and to a lesser extent in the middle layer of the granulation tissue 21 days after MI. The enhanced DGKzeta expression in the infarcted and border areas could be attributed to granulocytes and macrophages. In contrast, the expression of DGKepsilon in the infarcted and border areas was lower than that in the viable left ventricle (LV) throughout the postoperation period. Furthermore, DGKepsilon expression in the viable myocardium 21 days after MI decreased significantly compared with left ventricular myocardium in the sham-operated rats and was completely restored by treatment with captopril. Our results demonstrate that three DGK isozymes are expressed in the heart and that each isozyme might have different functional characteristics in the healing and LV remodeling after MI.