tbuckley/cabot-search huggingface dataset:
Cardiovascular Disease Mortality After Chemotherapy or Surgery for Testicular Nonseminoma: A Population-Based Study
Authors: Chunkit Fung, Sophie D. Fossa, Michael T. Milano, Deepak M. Sahasrabudhe, Derick R. Peterson, Lois B. Travis
Journal: Journal of Clinical Oncology (2015)

Purpose Increased risks of incident cardiovascular disease (CVD) in patients with testicular cancer (TC) given chemotherapy in European studies were largely restricted to long-term survivors and included patients from the 1960s. Few population-based investigations have quantified CVD mortality during, shortly after, and for two decades after TC diagnosis in the era of cisplatin-based chemotherapy. Patients and Methods Standardized mortality ratios (SMRs) for CVD and absolute excess risks (AERs; number of excess deaths per 10,000 person-years) were calculated for 15,006 patients with testicular nonseminoma reported to the population-based Surveillance, Epidemiology, and End Results program (1980 to 2010) who initially received chemotherapy (n = 6,909) or surgery (n = 8,097) without radiotherapy and accrued 60,065 and 81,227 person-years of follow-up, respectively. Multivariable modeling evaluated effects of age, treatment, extent of disease, and other factors on CVD mortality. Results Significantly increased CVD mortality occurred after chemotherapy (SMR, 1.36; 95% CI, 1.03 to 1.78; n = 54) but not surgery (SMR, 0.81; 95% CI, 0.60 to 1.07; n = 50). Significant excess deaths after chemotherapy were restricted to the first year after TC diagnosis (SMR, 5.31; AER, 13.90; n = 11) and included cerebrovascular disease (SMR, 21.72; AER, 7.43; n = 5) and heart disease (SMR, 3.45; AER, 6.64; n = 6). In multivariable analyses, increased CVD mortality after chemotherapy was confined to the first year after TC diagnosis (hazard ratio, 4.86; 95% CI, 1.25 to 32.08); distant disease (P &lt; .05) and older age at diagnosis (P &lt; .01) were independent risk factors. Conclusion This is the first population-based study, to our knowledge, to quantify short- and long-term CVD mortality after TC diagnosis. The increased short-term risk of CVD deaths should be further explored in analytic studies that enumerate incident events and can serve to develop comprehensive evidence-based approaches for risk stratification and application of preventive and interventional efforts.
Mitogen-Induced Blastogenesis and Receptor Mobility Inhibition by Breast Cancer Serum With Elevated Orosomucoid (α&lt;sub&gt;1&lt;/sub&gt;-Acid Glycoprotein) Levels&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: D A Cheresh, J A Distasio, C L Vogel, D M Lopez
Journal: JNCI Journal of the National Cancer Institute (1982)

Sera from cancer patients have been shown to suppress normal lymphoid cell responsiveness in vitro. In the present study, sera from breast cancer patients were demonstrated to be inhibitory to the concanavalin A (Con A)-, Proteus vulgaris-derived phytohemaglutinin-, and pokeweed mitogen-induced blastogenic responses of normal lymphoid cells. Orosomucoid (OR) (α1-acid glycoprotein), an acutephase reactant, was elevated in these sera, and a positive correlation existed between the OR level in the sera and its immunosuppressive capacity. When normal lymphoid cells were reacted in fluorescein isothiocyanate-Iabeled Con A, cells that had been preincubated in breast cancer sera known to contain an elevated level of OR showed a significant decrease in Con A receptor mobility as compared to the receptor mobility of the same lymphoid cells preincubated in normal sera. Thus a component(s) from the sera of breast cancer patients had the capacity to inhibit lymphocyte activation. This inhibition might have resulted from an interaction of OR with the cell membrane.
Immunohistochemical localisation of protein tyrosine kinase receptors Tie-1 and Tie-2 in synovial tissue of rheumatoid arthritis: correlation with angiogenesis and synovial proliferation
Authors: T. Uchida
Journal: Annals of the Rheumatic Diseases (2000)

To investigate the involvement of Tie-1 and Tie-2, receptor tyrosine kinases required for angiogenesis, in synovial proliferation and angiogenesis of rheumatoid arthritis (RA).Synovial tissues from 10 patients with RA and three control subjects were analysed by double immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR).Expression of Tie-1 and Tie-2 was seen in all synovia, but predominantly in papillary projected portions. In synovial lining cells, Tie-2 was expressed mainly in the basal layer and frequently colocalised with vimentin and proliferating cell nuclear antigen (PCNA), whereas Tie-1 was also expressed in the superficial layer. In stromal cells, Tie-2 immunoreactivity was restricted to vimentin positive fibroblast-but not macrophage derived cells, whereas Tie-1 expression was not dependent on the phenotype. Tie receptors were also highly expressed in the endothelium and surrounding pericytes of capillaries scattered over the papillary proliferated synovium without notable difference in the expression of the two receptors. Furthermore, Tie positive vessels often overexpressed PCNA. In normal synovia, expression of Tie receptors was restricted to the capillary endothelium. RT-PCR confirmed the expression of Tie-1 and Tie-2 in RA synovial tissues and also in the cultured synoviocytes.The results suggest the possible involvement of overexpressed Tie-1 and Tie-2 in synovial lining and stromal cells in the pathophysiology of RA synovitis, probably through distinct mechanisms. Furthermore, expression of Tie receptors in actively growing vasculature may reflect the direct involvement of these receptors in angiogenesis and subsequent vascularisation.
Barbering in mice: a model for trichotillomania
Authors: Biji T Kurien, Tim Gross, R Hal Scofield
Journal: BMJ (2005)

Barbering (excessive grooming causing hair loss) in mice resembles trichotillomania (uncontrollable hair pulling) in humans in several respects and may be a useful model of trichotillomania, especially for investigating the complex genetic and environmental interactions Our interest in systemic lupus erythematosus led us to develop an animal model of lupus by immunising rabbits or mice with peptides that are targets of autoimmune sera from people with lupus.Animals immunised with these peptides developed autoimmunity to the entire Ro ribonucleoprotein as well as to other autoantigens.1–3 During this study, we observed the loss of facial hair in a groupof five experimental mice, possibly a sign of alopecia, a symptom of lupus. When we observed the characteristics of the hair loss and the fact that one of the mice had not lost her facial hairwhereas the other four had, we realised that this was a clear case of "barbering." Fur and whisker trimming by laboratory mice is referred to as "barbering." Laboratory mice housed in groups are frequently found with their facial hair and whiskers removed (figure). In one study facial alopecia was found in three of four adult female Fisher 344 rats that shared a cage for two months.4 The hairless areas were non-pruritic and without any association with pathogenic skin bacteria, dermatophytes, or ectoparasites. The authors found that when the unaffected rat was placed with a different set of rats, facial alopecia became evident in those animals within six days, and the hair of the original cagemates grew back within 21 days. Thus the alopecia was found to be caused by a dominant female "barber."4
Effect of glucocorticosteroid injections in tennis elbow verified on colour Doppler ultrasonography: evidence of inflammation
Authors: T E Torp-Pedersen, S T Torp-Pedersen, E Qvistgaard, H Bliddal
Journal: British Journal of Sports Medicine (2008)

Objectives: It has previously been reported that lateral epicondylitis may be diagnosed with colour Doppler ultrasonography (US) by detecting hyperaemia inside the common extensor origin (CEO).This study reports on the association between Doppler US findings and the short-term response of US-guided corticosteroid injection in patients with LE. Design: Case-only, blinded intervention study. Setting: Secondary care at a government hospital. Patients: 62 patients with LE verified by colour Doppler US. Intervention: One US-guided corticosteroid injection was given into the CEO. Main outcome measures: Patients were evaluated at baseline before the injection and at 2 weeks of follow-up. Outcome measures were changes in pain score and US parameters (resistive index (RI) and the amount of colour within the CEO). Prognosticators for outcome were: use of computer mouse, symptom duration, elbow strain, RI, colour fraction, Likert pain score, pain at rest, pain during activity, age, height, weight, disease in dominant versus nondominant arm. Results: All but one patient experienced improvement of general elbow pain perception at follow-up at 2 weeks. In parallel, Doppler US showed significant reduction in colour fraction (mean (standard deviation) with 95% confidence limits: baseline 0.14 (0.10), at follow-up 0.02 (0.02), p&lt;0.0001). All but five patients showed a decrease in colour fraction; 74% decreased to 0. No clinical or US parameter could distinguish responders from non-responders. Conclusion: Corticosteroid injection has a marked short-term effect on pain and Doppler parameters. The reduction in hyperaemia mediated by an anti-inflammatory drug can be interpreted as evidence of an inflammatory component in LE.
Contribution of Degradation Products to the Anticancer Activity of Curcumin
Authors: Liang Shen, Hong-Fang Ji
Journal: Clinical Cancer Research (2009)

To the Editors: The recent interesting article by Dhillon et al. (1) evaluated the clinical biological effects of curcumin against advanced pancreatic cancer. One important puzzle arising from this study involves how the biological activities are done with the precondition of the low nanogram levels of circulating curcumin (only 22-41 ng/mL were detectable in plasma even at oral dose of 8 g/d; ref. 1). More efforts are needed to shed new light on the pharmacology of curcumin.Curcumin possesses low stability under various conditions; for example, about 90 decomposed within 30 minutes when curcumin was incubated in 0.1 mol/L phosphate buffer and serum-free medium (pH 7.2) at 37C (2). Curcumin is degraded to the bioactive compounds such as ferulic acid and vanillin (2), which may contribute to the observed biological activities of curcumin based on the following two aspects. Firstly, the degradation products overcome the limitation of the extremely poor aqueous solubility for parent curcumin as reflected by their respective logP (1.42 for ferulic acid and 1.09 for vanillin, much lower than those of the keto and enol isomers of curcumin, 2.56 and 2.17). Secondly, the degradation products have been proved to exhibit anticancer potentials through inhibiting the important targets involved in the development of cancer (35). For instance, it was reported that ferulic acid can inhibit effectively both the cyclooxygenase-1 and cyclooxygenase-2 enzymes (3) and significantly suppress NF-B activation (4). Vanillin can also inhibit NF-B activation and cyclooxygenase-2 gene expression (5).Therefore, it is reasonable to postulate that the bioactive degradation products should play important roles in the anticancer effects of curcumin, which may account, at least in part, for the observed biological activity with the almost detectable concentration of parent curcumin. In addition, in view of the extremely limited bioavailability of curcumin in various clinical trials, the contributions of the degradation products should be given full attention when elucidating the pharmacology of the versatile natural product in various diseases.The authors have declared no conflicts of interest.
Somatic Profiling of the Epidermal Growth Factor Receptor Pathway in Tumors from Patients with Advanced Colorectal Cancer Treated with Chemotherapy ± Cetuximab
Authors: Christopher G. Smith, David Fisher, Bart Claes, Timothy S. Maughan, Shelley Idziaszczyk, Gilian Peuteman, Rebecca Harris, Michelle D. James, Angela Meade, Bharat Jasani, Richard A. Adams, Sarah Kenny, Richard Kaplan, Diether Lambrechts, Jeremy P. Cheadle
Journal: Clinical Cancer Research (2013)

To study the somatic molecular profile of the EGF receptor (EGFR) pathway in advanced colorectal cancer, its relationship to prognosis, the site of the primary and metastases, and response to cetuximab.
Sustained activation of c-Jun N-terminal and extracellular signal-regulated kinases in port-wine stain blood vessels
Authors: Wenbin Tan, Margarita Chernova, Lin Gao, Victor Sun, Huaxu Liu, Wangcun Jia, Stephanie Langer, Gang Wang, Martin C. Mihm, J. Stuart Nelson
Journal: Journal of the American Academy of Dermatology (2014)
Sox4-Deficiency Syndrome in Mice Is an Animal Model for Common Trunk
Authors: Jing Ya, Marco W. Schilham, Piet A. J. de Boer, Antoon F. M. Moorman, Hans Clevers, Wouter H. Lamers
Journal: Circulation Research (1998)

Embryonic mice lacking functional Sox4 transcription factor die from cardiac failure at embryonic day (ED) 14. Heart morphogenesis in these embryos was analyzed in hematoxylin-azophlochsin or immunohistochemically stained, 3-dimensionally reconstructed serial sections between ED12 and ED14. Although Sox4 is expressed in the endocardially derived tissue of both the outflow tract and atrioventricular canal, Sox4-deficient hearts only suffer from defective transformation of the endocardial ridges into semilunar valves and from lack of fusion of these ridges, usually resulting in common trunk, although the least affected hearts should be classified as having a large infundibular septal defect. The more serious cases are, in addition, characterized by an abnormal number and position of the semilunar valve-leaflet anlagen, a configuration of the ridges typical for transposition of the great arteries (with linear rather than spiral course of both ridges and posterior position of the pulmonary trunk at the level of the valve), and variable size of the aorta relative to the pulmonary trunk. The coronary arteries always originated from the aorta, irrespective of its position relative to the pulmonary trunk. The restriction of the malformations to the arterial pole implies that the interaction between the endocardially derived tissue of the outflow tract and the neural crest-derived myofibroblasts determines proper development of the arterial pole.
Collaborative Care for Patients with Depression and Chronic Illnesses
Authors: Wayne J Katon, Elizabeth H B Lin, Michael Von Korff, Paul Ciechanowski, Evette J Ludman, Bessie Young, Do Peterson, Carolyn M Rutter, Mary McGregor, David McCulloch
Journal: New England Journal of Medicine (2010)

Patients with depression and poorly controlled diabetes, coronary heart disease, or both have an increased risk of adverse outcomes and high health care costs. We conducted a study to determine whether coordinated care management of multiple conditions improves disease control in these patients.
Effects of progressive myocardial ischaemia on systolic function, diastolic dysfunction, and load dependent relaxation
Authors: B J Leone, R M Norris, A Safwat, P Foëx, W A Ryder
Journal: Cardiovascular Research (1992)

The aims were to determine (1) the relationship between changes in contractile function (systolic shortening) and the appearance of diastolic dysfunction (postsystolic shortening) during progressive regional left ventricular ischaemia; (2) the effects of increased afterload (acute constriction of the descending thoracic aorta) on ischaemic contractile dysfunction; and (3) the effects of loading during ischaemia on load dependent relaxation.Regional myocardial function, using sonomicrometry, was measured in the short and long axes of the apex of the left ventricle of eight open chest anaesthetised dogs (16-20 kg). Progressive apical ischaemia was induced by graded reductions in left anterior descending coronary artery flow (critical constriction, ischaemia 1, ischaemia 2, total coronary occlusion, and postocclusive maximum reactive hyperaemia). Acute afterloading was induced by a snare placed around the descending aorta.Consistent decreases in systolic shortening and increases in postsystolic shortening relative to the total segmental shortening in the short axis of the apical region were seen with worsening ischaemia. Aortic constriction increased the magnitude of apical postsystolic shortening and decreased apical systolic shortening in the short axis during critical constriction, ischaemia 1, and ischaemia 2. Long axis function changed in a qualitatively similar but quantitatively different manner. There was a significant decrease in the load dependency of relaxation with total coronary occlusion.(1) Changes in systolic and diastolic function occurred concomitantly as mild regional myocardial ischaemia developed and intensified; (2) afterloading significantly worsened regional systolic and diastolic dysfunction during mild ischaemia; and (3) progression of regional ischaemia resulted in loss of load dependent relaxation.
Duodenal nutrient exclusion improves metabolic syndrome and stimulates villus hyperplasia
Authors: Kirk M Habegger, Omar Al-Massadi, Kristy M Heppner, Andriy Myronovych, Jenna Holland, Jose Berger, Chun-Xia Yi, Yuanging Gao, Maarit Lehti, Nickki Ottaway, Sarah Amburgy, Christine Raver, Timo D Müller, Paul T Pfluger, Rohit Kohli, Diego Perez-Tilve, Randy J Seeley, Matthias H Tschöp
Journal: Gut (2013)

<h3>Objective</h3> Surgical interventions that prevent nutrient exposure to the duodenum are among the most successful treatments for obesity and diabetes. However, these interventions are highly invasive, irreversible and often carry significant risk. The duodenal-endoluminal sleeve (DES) is a flexible tube that acts as a barrier to nutrient-tissue interaction along the duodenum. We implanted this device in Zucker Diabetic Fatty (ZDF) rats to gain greater understanding of duodenal nutrient exclusion on glucose homeostasis. <h3>Design</h3> ZDF rats were randomised to four groups: Naive, sham ad libitum, sham pair-fed, and DES implanted. Food intake, body weight (BW) and body composition were measured for 28 days postoperatively. Glucose, lipid and bile acid metabolism were evaluated, as well as histological assessment of the upper intestine. <h3>Results</h3> DES implantation induced a sustained decrease in BW throughout the study that was matched by pair-fed sham animals. Decreased BW resulted from loss of fat, but not lean mass. DES rats were also found to be more glucose tolerant than either ad libitum-fed or pair-fed sham controls, suggesting fat mass independent metabolic benefits. DES also reduced circulating triglyceride and glycerol levels while increasing circulating bile acids. Interestingly, DES stimulated a considerable increase in villus length throughout the upper intestine, which may contribute to metabolic improvements. <h3>Conclusions</h3> Our preclinical results validate DES as a promising therapeutic approach to diabetes and obesity, which offers reversibility, low risk, low invasiveness and triple benefits including fat mass loss, glucose and lipid metabolism improvement which mechanistically may involve increased villus growth in the upper gut.
Canonical Nlrp3 Inflammasome Links Systemic Low-Grade Inflammation to Functional Decline in Aging
Authors: Yun-Hee Youm, Ryan W. Grant, Laura R. McCabe, Diana C. Albarado, Kim Yen Nguyen, Anthony Ravussin, Paul Pistell, Susan Newman, Renee Carter, Amanda Laque, Heike Münzberg, Clifford J. Rosen, Donald K. Ingram, J. Michael Salbaum, Vishwa Deep Dixit
Journal: Cell Metabolism (2013)
Pulmonary hypertension in lymphangioleiomyomatosis: characteristics in 20 patients
Authors: Vincent Cottin, Sergio Harari, Marc Humbert, Hervé Mal, Peter Dorfmüller, Xavier Jaïs, Martine Reynaud-Gaubert, Grégoire Prevot, Romain Lazor, Camille Taillé, Jacques Lacronique, Sabrina Zeghmar, Gérald Simonneau, Jean-François Cordier
Journal: European Respiratory Journal (2012)

This retrospective, multicentre study evaluated patients with lymphangioleiomyomatosis (LAM) and pre-capillary pulmonary hypertension (PH) by right heart catheterisation. It was conducted in 20 females with a mean±sd age of 49±12 yrs and a mean±sd time interval between LAM and PH diagnoses of 9.2±9.8 yrs. All, except for one patient, were receiving supplemental oxygen. 6-min walking distance was mean±sd 340±84 m. Haemodynamic characteristics were: mean pulmonary artery pressure (PAP) 32±6 mmHg, cardiac index 3.5±1.1 L·min<sup>−1</sup>·m<sup>−2</sup> and pulmonary vascular resistance (PVR) 376±184 dyn·s·cm<sup>−5</sup>. Mean PAP was &gt;35 mmHg in only 20% of cases. The forced expiratory volume in 1 s was 42±25%, carbon monoxide transfer factor was 29±13%, and arterial oxygen tension (<i>P</i><sub>a,O<sub>2</sub></sub>) was 7.4±1.3 kPa in room air. Mean PAP and PVR did not correlate with <i>P</i><sub>a,O<sub>2</sub></sub>. In six patients who received oral pulmonary arterial hypertension (PAH) therapy, the PAP decreased from 33±9 mmHg to 24±10 mmHg and the PVR decreased from 481±188 dyn·s·cm<sup>−5</sup> to 280±79 dyn·s·cm<sup>−5</sup>. The overall probability of survival was 94% at 2 yrs. Pre-capillary PH of mild haemodynamic severity may occur in patients with LAM, even with mild pulmonary function impairment. PAH therapy might improve the haemodynamics in PH associated with LAM.
High Prevalence and Adverse Effect of Hepatitis C Virus Infection in Type II Diabetic-Related Nephropathy
Authors: JUN SOMA, TAKAO SAITO, YOSHIO TAGUMA, SHIGEMI CHIBA, HIROSHI SATO, KAZUHIKO SUGIMURA, SUSUMU OGAWA, SADAYOSHI ITO
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Over a 4-yr period in the northeast region of Japan (Tohoku), 3643 patients for whom a renal biopsy was available were screened. In addition, 2370 biopsied patients for whom hepatitis C virus (HCV) serology was available were evaluated. The prevalence of HCV infection was investigated in the 2370 biopsied patients. The highest prevalence of HCV infection was found in type II diabetic-related glomerulosclerosis (II-DGS) (24 of 123; 19.5%). At renal biopsy, clinical and laboratory findings and histologic parameters were comparable between the HCV-positive and -negative II-DGS groups. After renal biopsy, the decline of renal function reflected by the slope of reciprocal serum creatinine (1/S Cr ) was significantly greater in the HCV-positive group than in the HCV-negative group ( P = 0.001). The log-rank test performed on the renal survival curves showed a significant difference in the two groups ( P = 0.019). According to a multiple linear regression analysis adjusted for the effect of age, gender, BP, HbA1c, urinary protein excretion, and histologic parameters as covariates, urinary protein excretion ( P = 0.011), severe arteriolar hyalinosis ( P = 0.006), and HCV infection ( P &lt; 0.001) were significantly associated with 1/S Cr slope. Finally, HCV infection was randomly examined in 545 outpatients and inpatients with type II diabetes mellitus who did not undergo renal biopsy. Of these, 56 patients were positive for HCV antibody (10.3%), and their proteinuria was heavier than in 489 HCV-negative patients ( P = 0.001). This study reveals that HCV infection is present at a high rate in type II diabetic-related nephropathy and may have an adverse effect on the progression of the disease.