tbuckley/cabot-search huggingface dataset:
Nitrolinoleate Inhibits Superoxide Generation, Degranulation, and Integrin Expression by Human Neutrophils
Authors: Barbara Coles, Allison Bloodsworth, Stephen R. Clark, Malcolm J. Lewis, Andrew R. Cross, Bruce A. Freeman, Valerie B. O’Donnell
Journal: Circulation Research (2002)

Nitration of unsaturated fatty acids such as linoleate by NO-derived reactive species forms novel derivatives (including nitrolinoleate [LNO 2 ]) that can stimulate smooth muscle relaxation and block platelet activation by either NO/cGMP or cAMP-dependent mechanisms. Here, LNO 2 was observed to inhibit human neutrophil function. LNO 2 , but not linoleic acid or the nitrated amino acid 3-nitrotyrosine, dose-dependently (0.2 to 1 μmol/L) inhibited superoxide (O 2 ·− ) generation, Ca 2+ influx, elastase release, and CD11b expression in response to either phorbol 12-myristate 13-acetate or N -formyl-Met-Leu-Phe. LNO 2 did not elevate cGMP, and inhibition of guanylate cyclase by 1 H -[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one did not restore neutrophil responses, ruling out a role for NO. In contrast, LNO 2 caused elevations in intracellular cAMP in the presence and absence of phosphodiesterase inhibition, suggesting activation of adenylate cyclase. Compared with phorbol 12-myristate 13-acetate–activated neutrophils, N -formyl-Met-Leu-Phe–activated neutrophils were more susceptible to the inhibitory effects of LNO 2 , indicating that LNO 2 may inhibit signaling both upstream and downstream of protein kinase C. These data suggest novel signaling actions for LNO 2 in mediating its potent inhibitory actions. Thus, nitration of lipids by NO-derived reactive species yields products with antiinflammatory properties, revealing a novel mechanism by which NO-derived nitrated biomolecules can influence the progression of vascular disease.
Posttransplant primary CNS lymphoma
Authors: T. G. Phan, B. P. O'Neill, P. J. Kurtin
Journal: Neuro-Oncology (2000)

The records and neuro-imaging studies of 8 cases of post-transplant primary CNS lymphoma (PT-PCNSL) diagnosed at Mayo Clinic Rochester between 1970 and 1998 were reviewed retrospectively. All patients received organ transplantation. Patients who had hematologic transplantation were not included in the analysis. The median and mean age of the 4 men and 4 women was 45 years (range, 34 to 50 years). The median duration of symptoms before diagnosis was 36 days (range, 5 to 98 days). At diagnosis, the neurologic examination was focally abnormal in 6 of 8 patients. Compared with the initial computed tomographic study, MRI showed 25 additional brain lesions. Only 43.7% of lesions enhanced with contrast agent; of those that did, all but one were heterogeneous. Ependymal contact occurred in 5 patients. MRI lesion burden increased proportionally to the interval between scans. Diagnostic tissue was obtained by stereotactic biopsy from 6 patients and by open biopsy from 2. Hemorrhage occurred in the biopsy area in 4 patients who had stereotactic biopsy and 2 died (all had normal coagulation studies). Slides available for review (7 patients) showed that the tumors were of CD20-positive lineage and were positive for Epstein-Barr virus, using in situ hybridization. Six patients died. Median survival for the cohort was 13 weeks. PT-PCNSL has clinical and imaging features distinct from typical PCNSL. In our series, (1) PT-PCNSL presented nonspecifically and progressed rapidly, (2) stereotactic brain biopsy had significant morbidity, and (3) despite multimodal therapy, survival was poor.
Role of Primary Cilia in the Pathogenesis of Polycystic Kidney Disease
Authors: Bradley K Yoder
Journal: Journal of the American Society of Nephrology (2007)

Cysts in the kidney are among the most common inherited human pathologies, and recent research has uncovered that a defect in cilia-mediated signaling activity is a key factor that leads to cyst formation. The cilium is a microtubule-based organelle that is found on most cells in the mammalian body. Multiple proteins whose functions are disrupted in cystic diseases have now been localized to the cilium or at the basal body at the base of the cilium. Current data indicate that the cilium can function as a mechanosensor to detect fluid flow through the lumen of renal tubules. Flow-mediated deflection of the cilia axoneme induces an increase in intracellular calcium and alters gene expression. Alternatively, a recent finding has revealed that the intraflagellar transport 88/polaris protein, which is required for cilia assembly, has an additional role in regulating cell-cycle progression independent of its function in ciliogenesis. Further research directed at understanding the relationship between the cilium, cell-cycle, and cilia-mediated mechanosensation and signaling activity will hopefully provide important insights into the mechanisms of renal cyst pathogenesis and lead to better approaches for therapeutic intervention.
Endothelial cell seeding influences lesion development following arterial injury in the cholesterol-fed rabbit
Authors: M Conte
Journal: Cardiovascular Research (2002)

Objective: A functionally intact endothelial monolayer is thought to be critical for the adaptive process of vascular remodeling. This study was undertaken to examine the hypothesis that endothelial restoration is a critical determinant of remodeling after balloon angioplasty. Methods: Rabbits (N=12) were fed a cholesterol-supplemented diet (0.5%) and were subjected to bilateral balloon catheter injury of the iliofemoral arteries. At the time of injury, autologous venous endothelial cells (ECs) were implanted on one artery; the contralateral vessel served as control. A mean of 42 days after injury, arteriography was performed, followed by vessel harvest and histologic analysis. Results: High grade (≥70%) stenoses or occlusion were present in 55% of control and none of the EC-seeded arteries. EC-seeding was associated with improved mean (1.0±0 vs. 0.7±0.1, P<0.001) and minimal (0.7±0.1 vs. 0.4±0.1, P<0.001) luminal diameters by angiography. Seeded arteries demonstrated decreased medial area (0.69±0.04 vs. 1.04±0.09 mm2, P<0.001), a more uniform range of final lumen area (P<0.0001), and a positive remodeling index. Neointimal area was not significantly different. Stenoses were characterized primarily by larger neointimal area (2.02±0.18 vs. 1.38±0.09 mm2, stenotic vs. non-stenotic, P<0.005). Final lumen area was strongly influenced by both neointimal growth and vessel remodeling. Conclusions: These data support the concept that endothelial restoration is a critical determinant of the outcome of vessel wall repair, particularly in the context of hypercholesterolemia.
Perceptions of retired professional soccer players about the provision of support services before and after retirement
Authors: S Drawer, CW Fuller
Journal: British Journal of Sports Medicine (2002)

Objective: To determine the views of retired players about the provision of support services in English professional soccer before and after retirement and to assess the impact of career ending injury on these views. Method: An anonymous self administered questionnaire was distributed to 500 former players registered with the English Professional Footballers' Association. The questions asked about personal details, current medical status, reasons for retirement, perceptions of the provision and quality of support services, and use of prophylactic treatments while injured. Results: Of the 500 questionnaires distributed, 185 (37%) were returned. The Professional Footballers' Association provided significantly (p&lt;0.001) more help and advice to retired players on medical, financial, career, and educational matters than any other organisation. Although respondents showed some satisfaction with the provision of medical support, they were significantly (p&lt;0.001) less satisfied with the provision of sports science (23%) and education/welfare (19%) support. Respondents who had retired through injury, however, were more dissatisfied with the provision of all services. Significantly (p&lt;0.001) more respondents agreed with the view that injuries would reduce income earning potential, contribute to medical problems, and restrict the duration of their playing career. Respondents who had been medically diagnosed with osteoarthritis were significantly more likely, at some time, to have regularly received steroid injections while injured. Conclusion: The results presented are consistent with other evidence that the provision of injury prevention and socioeconomic services at professional soccer clubs is inadequate. The soccer industry should therefore develop a long term strategy for managing the needs of players who are forced to retire through injury.
Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice
Authors: Scott A Yuzwa, Xiaoyang Shan, Bryan A Jones, Gang Zhao, Melissa L Woodward, Xiaojing Li, Yanping Zhu, Ernest J McEachern, Michael A Silverman, Neil V Watson, Cheng-Xin Gong, David J Vocadlo
Journal: Molecular Neurodegeneration (2014)

Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. It remains unknown, however, if O-GlcNAc can influence the formation of amyloid plaques in the presence of tau pathology.We treated double transgenic TAPP mice, which express both mutant human tau and amyloid precursor protein (APP), with a highly selective orally bioavailable inhibitor of the enzyme responsible for removing O-GlcNAc (OGA) to increase O-GlcNAc in the brain. We find that increased O-GlcNAc levels block cognitive decline in the TAPP mice and this effect parallels decreased β-amyloid peptide levels and decreased levels of amyloid plaques.This study indicates that increased O-GlcNAc can influence β-amyloid pathology in the presence of tau pathology. The findings provide good support for OGA as a promising therapeutic target to alter disease progression in Alzheimer disease.
Some Effects of Partial Pulmonary Valvectomy
Authors: NOBLE O. FOWLER, EDGAR P. MANNIX, WILLIAM NOBLE
Journal: Circulation Research (1956)

Partial pulmonary valvectomy was performed in 19 dogs. No change in pulmonary arterial pulse pressure was seen when less than one valvular cusp was removed; frequently no change was observed when an entire cusp was removed. Widening of the pulmonary arterial pulse pressure could be produced by removal of more than one cusp or by inducing pulmonary hypertension after removal of only one cusp. Observation as long as six months postoperatively revealed no evidence of right ventricular failure resulting from the operation.
Prospective Evaluation of Clonal Evolution During Long-Term Follow-Up of Patients With Untreated Early-Stage Chronic Lymphocytic Leukemia
Authors: Tait D. Shanafelt, Thomas E. Witzig, Stephanie R. Fink, Robert B. Jenkins, Sarah F. Paternoster, Stephanie A. Smoley, Kimberly J. Stockero, Danielle M. Nast, Heather C. Flynn, Renee C. Tschumper, Susan Geyer, Clive S. Zent, Tim G. Call, Diane F. Jelinek, Neil E. Kay, Gordon W. Dewald
Journal: Journal of Clinical Oncology (2006)

Retrospective studies suggest cytogenetic abnormalities detected by interphase fluorescent in situ hybridization (FISH) can identify patients with chronic lymphocytic leukemia (CLL) who will experience a more aggressive disease course. Other studies suggest that patients may acquire chromosome abnormalities during the course of their disease. There are minimal prospective data on the clinical utility of the widely used hierarchical FISH prognostic categories in patients with newly diagnosed early-stage CLL or the frequency of clonal evolution as determined by interphase FISH.Between 1994 and 2002, we enrolled 159 patients with previously untreated CLL (83% Rai stage 0/I) on a prospective trial evaluating clonal evolution by FISH. Patients provided baseline and follow-up specimens for FISH testing during 2 to 12 years.Chromosomal abnormalities detected by FISH at study entry predicted overall survival. Eighteen patients experienced clonal evolution during follow-up. The rate of clonal evolution increased with duration of follow-up with only one occurrence in the first 2 years (n = 71; 1.4%) but 17 occurrences (n = 63; 27%) among patients tested after 5+ years. Clonal evolution occurred among 10% of ZAP-70-negative and 42% of ZAP-70-positive patients at 5+ years (P = .008).This clinical trial confirms prospectively that cytogenetic abnormalities detected by FISH can predict overall survival for CLL patients at the time of diagnosis, but also suggests that many patients acquire new abnormalities during the course of their disease. Patients with higher ZAP-70 expression may be more likely to experience such clonal evolution. These findings have important implications for both clinical management and trials of early treatment for patients with high-risk, early-stage CLL.
MicroRNA-1 downregulation by propranolol in a rat model of myocardial infarction: a new mechanism for ischaemic cardioprotection
Authors: Yanjie Lu, Yong Zhang, Hongli Shan, Zhenwei Pan, Xuelian Li, Baoxin Li, Chaoqian Xu, Bisi Zhang, Fengmin Zhang, Deli Dong, Wuqi Song, Guofen Qiao, Baofeng Yang
Journal: Cardiovascular Research (2009)

The present study was designed to investigate whether the beneficial effects of β-blocker propranolol are related to regulation of microRNA miR-1. We demonstrated that propranolol reduced the incidence of arrhythmias in a rat model of myocardial infarction by coronary artery occlusion. Overexpression of miR-1 was observed in ischaemic myocardium and strikingly, administration of propranolol reversed the up-regulation of miR-1 nearly back to the control level. In agreement with its miR-1-reducing effect, propranolol relieved myocardial injuries during ischaemia, restored the membrane depolarization and cardiac conduction slowing, by rescuing the expression of inward rectifying K+ channel subunit Kir2.1 and gap junction channel connexin 43. Our results further revealed that the β-adrenoceptor–cAMP–Protein Kinase A (PKA) signalling pathway contributed to the expression of miR-1, and serum response factor (SRF), which is known as one of the transcriptional enhancers of miR-1, was up-regulated in ischaemic myocardium. Moreover, propranolol inhibited the β-adrenoceptor–cAMP–PKA signalling pathway and suppressed SRF expression. We conclude that the β-adrenergic pathway can stimulate expression of arrhythmogenic miR-1, contributing to ischaemic arrhythmogenesis, and β-blockers produce their beneficial effects partially by down-regulating miR-1, which might be a novel strategy for ischaemic cardioprotection.
Terminal complement proteins C5b-9 release basic fibroblast growth factor and platelet-derived growth factor from endothelial cells.
Authors: L R Benzaquen, A Nicholson-Weller, J A Halperin
Journal: The Journal of Experimental Medicine (1994)

Interactions between endothelium and vascular smooth muscle cells play a major role in the biology of the blood vessel wall. Growth factors released from endothelial cells control in part the normal and pathological proliferation of vascular smooth muscle cells. Endothelial deposits of C5b-9 proteins, the membrane attack complex of complement (MAC), have been found in a variety of pathological tissues in which cell proliferation is an early characteristic abnormality, including atherosclerosis. We have explored a possible bridging role for terminal complement C5b-9 proteins in eliciting focal signals for cell proliferation by releasing growth factors from endothelial cells. We found that both bovine aortic and human umbilical vein cells respond to the MAC by releasing basic fibroblast growth factor and platelet-derived growth factor. These mitogens stimulate DNA synthesis in Swiss 3T3, vascular smooth muscle, and glomerular mesangial cells. Based on these findings, we propose that complement-induced release of mitogens from endothelial cells is a novel pathogenic mechanism for proliferative disorders.
Erythromycin and diffuse panbronchiolitis.
Authors: H Koyama, D M Geddes
Journal: Thorax (1997)

Ion Transport Unit, resistant to bronchodilators than that of chronic lations and thus suggesting some genetic National Heart and Lung Institute, obstructive pulmonary disease. 5 component to the disease.However, this as- Imperial College,The disease has been reported to be more sociation is yet to be confirmed.In addition, Manresa Road,prevalent in men and most have never smoked.a relatively small number of familial cases has London SW3 6LR, UK H KoyamaThe peak incidence occurs in the fifth and sixth been reported thus far, 20 though it is not undecades, 6 though it can occur at any age of usual that some of the siblings of the patients Department of adult life. 7 The titre of the cold haemagglutinin have chronic sinusitis without chest lesions. RespiratoryMedicine, Royal Brompton is raised in most patients, 8 and the changes in Based on a detailed observation of a single Hospital, the titre reflect the therapeutic response to case, Kudoh et al noticed that erythromycin Sydney Street, some extent.Other laboratory abnormalities might be effective in treating patients with DPB London SW3 6NP, UK include raised erythrocyte sedimentation rate, and performed an open trial which showed D M Geddes positive C reactive protein (CRP) and positive the beneficial effect of low dose, long term
Regulation of cytotoxic T-cell reactivity to syngeneic tumors by the thymus.
Authors: C L Reinisch, S L Andrew
Journal: The Journal of Experimental Medicine (1978)

Adult thymectomy has been shown to result in the enhanced capacity of splenic T cells to respond to and lyse syngeneic tumor cells in vitro. In addition, T cells from thymectomized mice which kill syngeneic tumor cells do not lyse either normal lymphoid or mitogen-stimulated syngeneic lymphoblast target cells. These findings indicate that the thymus exports a subpopulation of T cells sensitive to adult thymectomy which regulates the generation of cytolytic T cells directed against syngeneic tumor cells.
Insulin Resistance Predicts Mortality in Nondiabetic Individuals in the U.S.
Authors: Karlee J. Ausk, Edward J. Boyko, George N. Ioannou
Journal: Diabetes Care (2010)

OBJECTIVE Insulin resistance is a suspected causative factor in a wide variety of diseases. We aimed to determine whether insulin resistance, estimated by the homeostasis model assessment for insulin resistance (HOMA-IR), is associated with all-cause or disease-specific mortality among nondiabetic persons in the U.S. RESEARCH DESIGN AND METHODS We determined the association between HOMA-IR and death certificate–based mortality among 5,511 nondiabetic, adult participants of the third U.S. National Health and Nutrition Examination Survey (1988–1994) during up to 12 years of follow-up, after adjustment for potential confounders (age, sex, BMI, waist-to-hip ratio, alcohol consumption, race/ethnicity, educational attainment, smoking status, physical activity, C-reactive protein, systolic and diastolic blood pressure, plasma total and HDL cholesterol, and triglycerides). RESULTS HOMA-IR was significantly associated with all-cause mortality (adjusted hazard ratio 1.16 [95% CI 1.01–1.3], comparing successive quartiles of HOMA-IR in a linear model and 1.64 [1.1–2.5], comparing the top [HOMA-IR &amp;gt;2.8] to the bottom [HOMA-IR ≤1.4] quartile). HOMA-IR was significantly associated with all-cause mortality only in subjects with BMI &amp;lt;25.2 kg/m2 (the median value) but not in subjects with BMI ≥25.2 kg/m2. Subjects in the second, third, and fourth quartile of HOMA-IR appeared to have higher cardiovascular mortality than subjects in the lowest quartile of HOMA-IR. HOMA-IR was not associated with cancer-related mortality. CONCLUSIONS HOMA-IR is associated with all-cause mortality in the nondiabetic U.S. population but only among persons with normal BMI. HOMA-IR is a readily available measure that can be used in the future to predict mortality in clinical or epidemiological settings.
Gene Transfer as an Approach to Treating Hemophilia
Authors: Katherine A. High
Journal: Circulation Research (2001)

Abstract —Hemophilia is an X-linked bleeding diathesis caused by a deficiency of either factor VIII or factor IX. Present treatment for hemophilia involves intravenous infusion of either recombinant or plasma-derived clotting factor concentrates. Problems with this treatment method, including the expense, need for intravenous access, and risks of blood-borne disease transmission, have fueled an interest in developing a gene-transfer approach to treatment. On the basis of experience with protein concentrate therapy, it seems likely that even modest elevations in circulating levels of factor VIII or factor IX can prevent most of the mortality and much of the morbidity associated with the disease. Hemophilia has a number of advantages as a model system for working out strategies for gene transfer as an approach to the treatment of genetic diseases; these include wide latitude in choice of target tissue, a wide therapeutic window for levels of circulating factor, ease of determining therapeutic endpoints, and existence of excellent animal models of the disease. Preclinical studies over the last decade have recently culminated in the initiation of clinical trials of gene transfer for hemophilia A and B. Three trials, each using different vectors and target tissues, are presently underway, and two additional trials are in late planning stages. This report reviews the preclinical data underlying these strategies and the design of the ongoing and proposed clinical trials.
Comments on 'Conception during "Diane" Therapy—a successful outcome'
Authors: P. Bye
Journal: British Journal of Dermatology (1986)

Journal Article Comments on ‘Conception during “Diane” Therapy—a successful outcome’ Get access P. Bye P. Bye Shering Chemicals Ltd., Burgess Hill, West Sussex RH15 9NE, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 114, Issue 4, 1 April 1986, Page 516, https://doi.org/10.1111/j.1365-2133.1986.tb02862.x Published: 01 April 1986
Handbook of Mentalizing in Mental Health Practiceedited by BatemanAnthony W., M.A., F.R.C.Psych. and FonagyPeter, Ph.D., F.B.A. Washington, DC, American Psychiatric Publishing, 2011, 617 pp., $69.00 (paper).
Authors: Lois W. Choi-Kain
Journal: American Journal of Psychiatry (2012)