tbuckley/cabot-search huggingface dataset:
Ventricular Systolic Septal Thickening and Excursion in Idiopathic Hypertrophic Subaortic Stenosis
Authors: Ronald M. Rossen, Daniel J. Goodman, Robert E. Ingham, Richard L. Popp
Journal: New England Journal of Medicine (1974)

Asymmetric septal hypertrophy has been described as the pathognomonic abnormality in idiopathic hypertrophic subaortic stenosis. It has been suggested that the ventricular septum is hypercontractile and accounts for the left ventricular outflow-tract obstruction. Twenty-nine patients with idiopathic hypertrophic subaortic stenosis were studied by cardiac ultrasound to determine the degree of systolic thickening and amplitude of excursion of the ventricular septum. In all patients septal thickening was significantly reduced from normal, with a range of 0 to 22 per cent (mean of 9.3 per cent). The excursion of the left ventricular septal echo ranged from 1 to 6 mm (mean of 4 mm) and was decreased from normal in 21 patients. Therefore, the septum does not appear to be a hypercontractile structure in this disorder. These results take issue with previously proposed pathophysiology and suggest that other hypotheses need further investigation. (N Engl J Med 291:1317–1319, 1974)
Abstract 2636: Preclinical evaluation of the Hsp90 inhibitor KW-2478 in combination with bortezomib as a treatment for multiple myeloma
Authors: Toshihiko Ishii, Takayuki Nakashima, Toshihiro Seike, Aiko Shudo, Shiro Akinaga, Shiro Soga, Yukimasa Shiotsu
Journal: Cancer Research (2010)

Abstract KW-2478 is a novel Hsp90 inhibitor with a new chemical structure and is under clinical investigation in multiple myeloma patients. Our previous study revealed that KW-2478 bind to N-terminal ATP/ADP pocket and thus inducing apoptosis in myeloma cells. Others have reported that bortezomib, a proteasome inhibitor, induces apoptosis of myeloma cells through increase of ER stress mediator protein such as Noxa. Since Hsp90 inhibition can also causes cellular stress, combining Hsp90 inhibitor and bortezomib may be of therapeutic benefit. In this study, we assessed the combined effect of KW-2478 with bortezomib using human myeloma cell lines. In OPM2/GFP cells, KW-2478 enhanced caspase activation of bortezomib in vitro and this effect was revealed to be mediated through synergistic induction of Noxa. Interestingly KW-2478 reduced bortezomib-induced level of another ER stress mediator, Puma in the same cells. To see if this in vitro effect is translated into in vivo setting, we evaluated combined anti-tumor activity of KW-2478 with bortezomib in s.c. inoculated NCI-H929 human myeloma model. In this model, twice weekly treatment of KW-2478 at the dose of 50 mg/kg (1/4 of MTD) showed synergistic anti-tumor effect with 1 mg/kg bortezomib, without significant body weight loss. Our previous studies showed that KW-2478 showed anti-tumor activity in bone marrow environment, the combined effect of KW-278 with bortezomib was further evaluated using an orthotopic myeloma model in which OPM2/GFP cells were i.v. inoculated. The combination of KW-2478 with bortezomib showed synergistic reduction of myeloma cells in bone marrow and this effect was reflected in a significant decrease in serum M protein level. Our results strongly suggested that combination of KW-2478 with bortezomib may exhibit the enhanced anti-tumor activity against human myeloma than bortezomib alone. Clinical study for combination of KW-2478 with bortzomib in myeloma patients is warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2636.
Abstract 2050: Plk1 phosphorylation of Orc2 promotes DNA replication under conditions of stress
Authors: Bing Song, X. Shawn Liu, Korbin Davis, Xiaoqi Liu
Journal: Cancer Research (2012)

Abstract Polo-like kinase 1 (Plk1) plays pivotal roles in mitosis, however, little is known about its function in S phase. In this study, we show that inhibition of Plk1 impairs DNA replication and results in slow S-phase progression in cultured cancer cells. We have identified Origin Recognition Complex 2 (Orc2), a member of the DNA replication machinery, as a Plk1 substrate and have shown that Plk1 phosphorylates Orc2 at Ser188 in vitro and in vivo. Furthermore, Orc2-S188 phosphorylation is enhanced when DNA replication is under challenge induced by UV, hydroxyurea, gemcitabine, or aphidicolin treatment; cells expressing the unphosphorylatable mutant (S188A) of Orc2 had defects in DNA synthesis under stress, suggesting that this phosphorylation event is critical to maintain DNA replication under stress. To dissect the mechanism pertinent to this observation, we showed that Orc2-S188 phosphorylation associates with DNA replication origin and that cells expressing Orc2-S188A mutant fail to maintain the functional pre-replicative complex (pre-RC) under DNA replication stress. Furthermore, the intra-S phase checkpoint is activated in Orc2-S188A-expressing cells to cause delay of S-phase progress. Our study suggests a novel role of Plk1 in facilitating DNA replication under conditions of stress to maintain genomic integrity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2050. doi:1538-7445.AM2012-2050
Abstract 914: The role of CD44 variant in the development of spasmolytic polypeptide-expressing metaplasia (SPEM) and gastric cancer
Authors: Takeyuki Wada, Osamu Nagano, Takatsugu Ishimoto, Hiroko Oshima, Masanobu Oshima, Takashi Masuko, Hideo Baba, Yuko Kitagawa, Hideyuki Saya
Journal: Cancer Research (2011)

Abstract CD44 is a marker of tumor-initiating cells in gastric cancer. However, the cause or consequence of elevated CD44 in such immature tumor cells is not known. Gastric carcinogenesis involves a transition from normal mucosa to gastritis, which then leads to metaplasia and eventually adenocarcinoma. Although the emergence of metaplasia or dysplasia is a key event of inflammation-related gastric carcinogenesis, the precise mechanism underlying the transition from normal gastric epithelium to metaplasia and cancer remains unsolved. Spasmolytic polypeptide (known as trefoil factor family 2)-expressing metaplasia (SPEM) results from a metaplastic change of gastric epithelial cells in response to chronic inflammation. Here we show that the trefoil factor family 2 (TFF2)+ metaplastic glands as well as gastric tumor glands contain CD44 variant isoform-expressing (CD44v+) cells in K19-Wnt1/C2mE mouse, a genetic mouse model for gastric tumorigenesis. Furthermore, the analysis of three transgenic mouse lines K19-Wnt1, K19-C2mE and K19-Wnt1/C2mE revealed that de novo expression of CD44v in SPEM cells is triggered by prostaglandin E2-mediated signaling. Isolated CD44-expressing tumor cells in K19-Wnt1/C2mE mice by fluorescence-activated cell sorting (FACS) manifested increased expression of SPEM-related genes, suggesting that metaplastic epithelium might give rise to both of CD44v+ tumor cells and CD44v+ SPEM cells in mice. To investigate the role of CD44 in the development of SPEM and gastric tumor in mice, we generated CD44-/- K19-Wnt1/C2mE mice. We found that CD44 ablation significantly suppresses the development of SPEM and gastric tumor, suggesting that CD44v+ cells play a key role in gastric tumorigenesis. Furthermore, we found that the emergence of CD44v+ SPEM glands adjacent to cancer is tightly associated with the CD44v-expressing gastric cancer formation in human. Our present study thus suggest that SPEM cells might be susceptible for oncogenesis due to their proliferative capacity and that CD44v+ SPEM cells are cells-of-origin for CD44v+ tumor-initiating cells in human gastric adenocarcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 914. doi:10.1158/1538-7445.AM2011-914
Abstract P3-12-02: Polymorphisms, Endogenous Hormone Levels and Breast Cancer Risk in Premenopausal Women
Authors: K Walker, N Johnson, C Palles, E Folkerd, SG Hillier, S Moss, L Gibson, M Dowsett, J Peto, I dos Santos Silva, O. Fletcher
Journal: Cancer Research (2010)

Abstract Background: Endogenous sex hormone levels are widely believed to be implicated in the etiology of breast cancer through indirect evidence such as early menarche and late menopause, and from direct evidence of an association between circulating levels and breast cancer risk in postmenopausal women. Epidemiological studies suggest that levels may be partly genetically determined, particularly in premenopausal women. Few studies have attempted to identify polymorphisms associated with endogenous hormone levels in premenopausal women, and their findings have been limited. Quantification of hormone levels in premenopausal women is difficult because of their cyclical nature. In particular, estrogen has a marked peak in the follicular phase and a further wider peak in the luteal phase. Methods: 789 healthy premenopausal women from the Mammography Oestrogens and Growth Factors (MOG) study and the British Breast Cancer (BBC-NCRN) study each provided a single blood sample and up to 7 urine samples. We developed a protocol designed to capture peak follicular phase urinary estrone glucuronide (E1G), and luteal phase E1G. Repeated measurements of creatinine-adjusted E1G levels were used to describe features of the E1G curve such as mean and peak follicular E1G, and luteal E1G. Endogenous sex hormone binding globulin (SHBG) and the androgens testosterone, androstenedione, dehydroepiandrosterone and dehydroepiandrosterone sulfate were measured on single plasma samples. 691 tagging SNPs capturing common variation in genes within the estrogen synthesis and metabolism pathways were successfully genotyped. Linear regression was used to evaluate the effect of each polymorphism on (log-transformed) measures of urinary E1G levels, SHBG levels and plasma androgen levels. Results: We identified a SNP with minor allele frequency of 7%, in which the minor allele was associated with a 20% reduction in circulating levels of E1G (P&amp;lt;10-8) in healthy premenopausal women. We are currently genotyping this SNP in 12,000 breast cancer cases and 12,000 controls to test whether the reduction in circulating estrogen levels affects breast cancer risk. Conclusions: Circulating hormone levels in premenopausal women may provide a useful intermediate phenotype in the search for low-penetrance breast cancer risk alleles. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-12-02.
The Optimal Duration of Anticoagulant Therapy for Venous Thrombosis
Authors: Jack Hirsh
Journal: New England Journal of Medicine (1995)

Over the past 20 years, the results of well-designed randomized trials in patients with deep-vein thrombosis have provided reliable information about the treatment of this common disorder. Patients with deep-vein thrombosis should receive adequate doses of heparin for a minimum of five days.13 When heparin is stopped, patients should continue to receive oral anticoagulant therapy; the incidence of recurrent deep-vein thrombosis in the first three months is over 25 percent without such treatment, but less than 4 percent among treated patients.4,5 Progress has been made in determining the optimal intensity of oral anticoagulant therapy,6 but the optimal duration . . .
Abstract 3817: Nitric oxide-donating aspirin induces G2/M phase cell cycle arrest in human cancer cells by regulating phase transition proteins
Authors: Li Gao, Jennie L. Williams
Journal: Cancer Research (2012)

Abstract NO-aspirin (NO-ASA), consisting of aspirin, a non-steroidal anti-inflammatory drug (NSAID), and a nitric oxide (NO)-releasing group, is reportedly safer than aspirin and effective in colon cancer chemoprevention. NO-ASA reduced the growth of several cancer cell lines much more potently than aspirin, with IC50 values at 24-h as follows: (a) colon (HT-29, SW480, HCT-15, and LoVo) 174 to 257 µM; (b) pancreas (BxPC-3), 175 µM; (c) skin (A431), 133 µM; (d) cervix (Hela), 240 µM; and (e) breast (MCF-7), 268 µM. In all instances, the IC50 values for the parent compound were &amp;gt;1,000 µM. To assess NO-ASA's mechanism of action, we studied in vitro its effect on colonocyte kinetics. In all cell lines examined, the growth inhibitory effect of NO-ASA was accompanied by cell cycle arrest in the G2/M phase transition. This inhibition directly correlated to altered expression of G2/M transition related proteins. Specifically, NO-ASA had a time- and concentration-dependent effect on the expression of cyclin D1. Here we propose that NO-ASA-mediated G2/M arrest is probably caused by ROS generation. This conclusion is based on (a) treatment with NO-ASA generates ROS in SW480 and (b) the G2/M arrest induced by NO-ASA is abolished on pretreatment with the antioxidant NAC. Thus, NO-ASA's superior effectiveness compared to traditional aspirin is due in part to its ability to induce G2/M phase cell cycle arrest in human cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3817. doi:1538-7445.AM2012-3817
Clinical repigmentation patterns in paediatric vitiligo
Authors: E.Y. Gan, T. Gahat, M. Cario-André, J. Seneschal, K. Ezzedine, A. Taïeb
Journal: British Journal of Dermatology (2016)

Repigmentation is an essential outcome measure in vitiligo. However, clinical studies describing vitiligo repigmentation patterns are lacking.To assess and clearly define the repigmentation patterns in a series of patients with vitiligo, correlating these with clinicoepidemiological characteristics.Patients with vitiligo seen at least at twice (initial consultation and follow-up visit) in the Department of Paediatric Dermatology, Hôpital Pellegrin des Enfants, Bordeaux University Hospital from 2006 to 2014 were included. Clinical photographs and case records were reviewed.There were 109 patients (64 female, 45 male) mostly with Fitzpatrick skin type III (n = 67, 61%). The majority had nonsegmental (n = 71, 65%) or segmental vitiligo (n = 29, 27%). In total 172 representative vitiligo lesions were analysed. Overall, a combined pattern of repigmentation was most commonly seen (n = 106, 62%). The combined pattern occurred more frequently in patients with segmental vs. nonsegmental vitiligo (P = 0·009), whereas the diffuse pattern was more frequent in the latter (P = 0·007). Diffuse repigmentation was the predominant pattern on the eyelids (P < 0·001). We observed a new pattern in sites with few to absent hair follicles, which we propose to call 'medium spotted repigmentation'. This begins as circular macules of repigmentation, wider than 5 mm in diameter, which, from the outset, are larger than the initial macules of perifollicular repigmentation. This study is limited by its retrospective nature and small sample size for subgroup assessment.The combined pattern of repigmentation was most frequently observed. Medium spotted repigmentation is a new pattern, which will benefit from larger studies for a better understanding.
Clinical and Biochemical Abnormalities in People Heterozygous for Hemochromatosis
Authors: Zaneta J. Bulaj, Linda M. Griffen, Lynn B. Jorde, Corwin Q. Edwards, James P. Kushner
Journal: New England Journal of Medicine (1996)

Ten percent of whites are heterozygous for the HLA-linked hemochromatosis mutation. We performed a cross-sectional analysis of 1058 genotyped heterozygotes to define the effects of age and sex on the phenotype.
Intramural hematoma of the colon after polypectomy – an unusual case occurrence
Authors: Shaoping Yu, Guangyao Wu, Zongquan Wen, Haiyan Huang
Journal: Endoscopy (2014)

A 43-year-old man was admitted to our hospital for polypectomy because of multiple colonic polyps. He had no history of hemorrhage or abdominal trauma, and was not being treated with anticoagulant therapy. His laboratory results, including coagulation testing, were all normal. A ball-like polyp was identified in the descending colon ([Fig. 1 a]) and was removed using a snare to leave a 10-mm peduncle. The remaining four small polyps (≤ 5 mm), located in the sigmoid colon and rectum, were removed using forceps.
Evaluation of Alpha-Cell Function by Infusion of Alanine in Normal, Diabetic and Obese Subjects
Authors: Jonathan K. Wise, Rosa Hendler, Philip Felig
Journal: New England Journal of Medicine (1973)

To evaluate alpha-cell function, L-alanine was infused intravenously (0.15 g per kilogram of body weight) to healthy controls, nonobese and obese diabetic patients and obese subjects with normal glucose tolerance. Alanine induced a consistent rise in plasma glucagon in normal subjects that was increased by starvation. An augmented glucagon response was also observed in nonobese diabetic patients. In contrast, the glucagon response was diminished in obese subjects, even in the presence of diabetes. No glucagon increment occurred in two diabetic patients with pancreatic insufficiency. For all subjects, the rise in plasma glucagon induced by alanine was directly proportional to the rise in plasma glucose. Thus, the alpha-cell response to alanine appears to be augmented in diabetes and starvation and suppressed by obesity, even when accompanied by diabetes. In each of these circumstances, the glucagon response is reflected in the rise in blood glucose. Infusion of alanine may provide a useful means of evaluating alpha-cell function in a variety of metabolic states.
Deletions of Interferon Genes in Acute Lymphoblastic Leukemia
Authors: Manuel O. Diaz, Charles M. Rubin, Alanna Harden, Sheryl Ziemin, Richard A. Larson, Michelle M. Le Beau, Janet D. Rowley
Journal: New England Journal of Medicine (1990)

Structural rearrangements involving the short arm of chromosome 9, including bands 9p21 and 22, are found in the leukemia cells of 7 to 13 percent of patients with acute lymphoblastic leukemia. The interferon-α gene cluster and the interferon-β1 gene have been localized to this chromosomal region. We have previously demonstrated deletions of these genes in several cell lines established in vitro from patients with lymphoblastic leukemia.
A10.16 Risk for lung cancer in ra and different ra phenotypes: Results from a population-based case-control study
Authors: K Chatzidionysiou, G Reynisdottir, V Joshua, T Frisell, J Askling, AI Catrina
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background&nbsp;and&nbsp;purpose</h3> It has been shown that patients with Rheumatoid Arthritis (RA) are at increased risk for certain malignancies, among them lung cancer. We aimed to investigate the association between lung cancer and different RA phenotypes based on rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA) status. <h3>Methods</h3> We used the population-based case-control study EIRA (Epidemiological Investigation of Risk factors for Rheumatoid Arthritis). Patients with RA diagnosis and controls (matched for age, sex, calendar period and area of residence) were included during 1996–2013. The data were linked to the Swedish nationwide cancer register. Cox regression was used to calculate RR. Due to the significant correlation between smoking and RA as well as presence of RF and ACPA, stratified analyses based on smoking status were performed, in order to account for effect modification. <h3>Results</h3> A total of 3547 RA patients and 5586 controls were included in the study. The mean age (SD) was 52 (13) years and the percentage of female was 72%. Significantly more RA patients than controls were diagnosed with lung cancer after RA diagnosis (58 vs. 26 per 100,000 patient-years, respectively, p = 0.002). RA itself gave twice an increased risk for developing lung cancer when adjusted for age and sex (RR=1.9, 95% CI=1.2–3.2, p = 0.01), but the statistical significance disappeared when smoking was included in the model. However, after stratification according to smoking status, RA was significantly associated to lung cancer development in never or ex-smokers (RR&nbsp;=&nbsp;2.4, 95% CI&nbsp;=1.0–6.2, p = 0.05) but not in current smokers (RR&nbsp;=1.2, 95% CI&nbsp;=&nbsp;0.6–2.3, p = 0.6). In RA patients, higher age, smoking, RF positivity, RF and/or ACPA positivity and double seropositivity were significant risk factors for lung cancer. In a stratified by smoking status analysis RF positivity was significantly associated to lung cancer in non-smokers. <h3>Conclusion</h3> In this study RA, especially RF positive RA, was associated to the development of lung cancer in never or ex-smokers. Although not statistically significant, patients who developed lung cancer were more often positive for RF and/or ACPA irrespective of smoking status.
EXOSOMES FROM THE HUMAN PLACENTA-DERIVED AMNIOTIC MESENCHYMAL STEM CELLS RESTORE THE INJURED MURINE MYOCARDIUM
Authors: Michelle Santoso, Morteza Mahmoudi, Atsushi Tachibana, Raymond G. Sierra, Tsutomu Matsui, Andrew Goldstone, Bryan Edwards, Soichi Wakatsuki, Joseph Woo, Phillip Yang
Journal: Journal of the American College of Cardiology (2016)
SP0166 How to Implement Systematic Cardio-Vascular Risk Assessment in Outpatients with Inflammatory Arthritis in Nursing Consultations in Accordance with the Eular Recommendations – A Danish Example
Authors: J. Primdahl
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> It is well known that patients9 with inflammatory arthritis (IA) have an increased risk for cardiovascular (CV) morbidity and mortality based on both the inflammatory process and the increased prevalence of some of the known risk factors for development of CV disease. In 2010 ten evidence based EULAR recommendations for CV management in patients with rheumatoid arthritis (RA) and other forms of IA was published (1). CV risk assessment in all patients with RA was recommended and should be considered for patients with other forms of IA based on national guidelines. This lecture will provide an overview of how we set out to implement these recommendations at a Danish hospital in patients with RA and other forms of IA. The patients9 pharmacological treatment and risk factors were assessed together with the patient in planned nurse-led consultations. The patients9 10-year mortality risk was calculated based on the European SCORE system (2). For patients with RA the risk score was adapted by a factor 1.5 if the patient met two of three defined criteria: 1) disease duration of more than 10 years, 2) rheuma-factor positivity and or anti-cyclic citrullinated peptide positivity and: 3) presence of certain extra-articular manifestations. The lecture will provide information about the specific content and delivery of the nurse-led assessments, how they were documented in the national database, Danbio and how the patients identified risk was managed subsequently. Opportunities for future development and research will be discussed. <h3>References</h3> Peters, M.J., et al., EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis, 2010; 69(2): p. 325-31. Conroy, R.M., et al., Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J, 2003; 24(11): p. 987-1003. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6217
LEFT VENTRICULAR DIFFUSE MYOCARDIAL FIBROSIS IN SURVIVORS OF TETRALOGY OF FALLOT REPAIR AND CORRELATION WITH MYOCARDIAL STRAIN BY CARDIAC MAGNETIC RESONANCE: INSIGHT INTO MECHANISM OF LEFT VENTRICULAR FUNCTION
Authors: Mark A. Fogel, Christine Li, Matthew Harris, Marc Keller, Frederick Epstein, Christopher Kramer, Kevin Whitehead
Journal: Journal of the American College of Cardiology (2016)