tbuckley/cabot-search huggingface dataset:
Chest pain in a patient with cystic fibrosis
Authors: D P Dunagan, S L Aquino, M S Schechter, B K Rubin, J W Georgitis
Journal: European Respiratory Journal (1998)

Case historyA 38 yr old female with a history of cystic fibrosis (CF) presented to an outside emergency department with dyspnoea and right-sided chest pain of approximately 12 h duration.Her history was significant for recurrent pneumothoraces and a recent respiratory exacerbation of CF requiring prolonged antibiotic therapy for Pseudomonas aeruginosa.She described the pain as relatively acute in onset, sharp, increased with deep inspiration, without outward radiation, and progressive in intensity.There was no history of travel, worsening cough, fever, chills or increase in her chronic expectoration of blood-streaked sputum.An outside chest radiograph was interpreted as demonstrating a "rounded" right lower lobe pneumonia and she was transferred to our institution for further evaluation.On examination, she was thin, afebrile and in minimal respiratory distress.There were decreased breath sounds throughout all lung fields, symmetric chest wall excursion with inspiration and bilateral basilar crackles.Subjective right lateral chest discomfort was reported with deep inspiratory manoeuvres.The remaining physical examination was normal except for clubbing of the upper extremities.Laboratory data revealed an elevated white blood cell count of 19.2×10 9 cells•L -1 with a normal differential.Haemoglobin and haematocrit were normal, as were prothro-
Correlation of Vascular Endothelial Growth Factor Expression and Microvessel Density in Cervical Intraepithelial Neoplasia
Authors: A Obermair, D Bancher-Todesca, S Bilgi, A Kaider, P Kohlberger, S Müllauer-Ertl, S Leodolter, G Gitsch
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: Angiogenesis (the formation of new blood vessels) appears to be required for the growth of invasive tumors, but little information exists about its role in the development of preinvasive lesions. We examined microvessel density and expression of vascular endothelial growth factor in specimens of cervical intraepithelial neoplasia (CIN), a preinvasive lesion of the uterine cervix, to determine whether a connection could be established between these parameters of angiogenesis and the grade of dysplasia (i.e., tissue abnormality). Methods: Sections of biopsy specimens from 83 patients with grades I–III CIN were examined retrospectively. Microvessels were localized by use of a polyclonal antibody directed against factor VIII-related antigen; vascular endothelial growth factor was detected by means of a monoclonal antibody. Reported P values are two-sided. Results: Highest microvessel densities and highest expression of vascular endothelial growth factor were found in a narrow border region between CIN lesions and the underlying stroma. A significant correlation was observed between high vascular endothelial growth factor expression and high microvessel density (Kendall's τ = 0.27; 95% confidence interval [CI] = 0.03–0.50; P = .018). Mean microvessel density values ± standard deviations for CIN I, CIN II, and CIN III lesions were 19.4 ± 5.8, 21.9 ± 7.0, and 34.1 ± 14.8, respectively (Kendall's τ = 0.46; 95% CI = 0.30–0.61; P<.0001). Corresponding values for vascular endothelial growth factor expression were 8.3 ± 3.5, 8.4 ± 2.0, and 12.2 ± 3.6, respectively (Kendall's τ = 0.41; 95% CI = 0.20–0.60; P<.0001). Conclusions: Our results are consistent with the idea that progression of cervical dysplasia is dependent on angiogenesis.
Exercise Capacity and Body Composition as Predictors of Mortality Among Men With Diabetes
Authors: Timothy S. Church, Yiling J. Cheng, Conrad P. Earnest, Carolyn E. Barlow, Larry W. Gibbons, Elisa L. Priest, Steven N. Blair
Journal: Diabetes Care (2004)

OBJECTIVE—To quantify the relation of fitness to mortality among men with diabetes, adjusted for BMI and within levels of BMI. RESEARCH DESIGN AND METHODS—In this observational cohort study, we calculated all-cause death rates in men with diabetes across quartiles of fitness and BMI categories. Study participants were 2,196 men with diabetes (average age 49.3 years, SD 9.5) who underwent a medical examination, including a maximal exercise test, during 1970 to 1995, with mortality follow-up to 31 December 1996. RESULTS—We identified 275 deaths during 32,161 person-years of observation. Risk of all-cause mortality was inversely related to fitness. For example, in the fully adjusted model, the risk of mortality was 4.5 (2.6–7.6), 2.8 (1.6–4.7), and 1.6 (0.93–2.76) for the first, second, and third fitness quartiles, respectively, with the fourth quartile (highest fitness level) as the referent (P for trend &amp;lt;0.0001). There was no significant trend across BMI categories for mortality after adjustment for fitness. Similar results were found when the fitness-mortality relation was examined within levels of body composition. In normal-weight men with diabetes, the relative risks of mortality were 6.6 (2.8–15.0), 3.2 (1.4–7.0), and 2.2 (1.1–4.6) for the first, second, and third quartiles of fitness, respectively, as compared with the fourth quartile (P for trend &amp;lt;0.0001). We found similar results in the overweight and obese weight categories. CONCLUSIONS—There was a steep inverse gradient between fitness and mortality in this cohort of men with documented diabetes, and this association was independent of BMI.
Current therapy of the failing heart.
Authors: J N Cohn
Journal: Circulation (1988)

Myocardial dysfunction eventuating in systolic and diastolic pump function abnormalities is a consequence of a wide variety of cardiac diseases. The symptoms that develop in this syndrome appear to be related as much to peripheral and neurohormonal mechanisms as to the underlying pathological and cardiac functional abnormality. Relief of symptoms, slowing of the progression of the cardiac functional abnormality, and prolongation of life provide the major agenda for the physician faced with the management of these patients. Judicious use of vasodilators, diuretics, digoxin, dietary therapy, and exercise therapy can relieve symptoms and improve the quality of life in most patients suffering from this syndrome. Recent evidence that vasodilator drugs can prolong life now provides the physician with further justification for routine use of this class of compounds. The eventual solution to the high mortality in this common disease process may be prevention of the development of overt heart failure by more prompt recognition and early treatment of the signs of ventricular dysfunction. This possibility must await the completion of current and proposed clinical trials.
Antipolysaccharide antibodies of restricted heterogeneity secreted by a single lymph node
Authors: H Frost, DG Braun, D Poskitt, RNP Cahill, Z Trnka
Journal: The Journal of Experimental Medicine (1976)

Immune responses which give rise to the synthesis of antibodies of restricted heterogeneity can be reproducibly induced in rabbits and mice by streptococcal polysaccharide antigens (1,2). While these reports have demonstrated clonotype restriction in the immune serum of rabbits and mice, they give little information with respect to the clontype restriction in a single reaction site of organized lymphoid tissue, for example a single lymph node. The kinetics of immune responses in lymph nodes in situ have been studied in sheep using a variety of antigens (3-6), and a substantial body of information is available on the changes in cell output, cell type, and the number of antibody-secreting cells which occur within the efferent lymph of antigen-stimulated lymph nodes. However, there is no information with respect to the amount and the heterogeneity of antibody that is secreted by the lymph node or cells within the efferent lymph. In the present report we have examined the temporal sequence of clonal restriction in the efferent lymph of individual sheep popliteal lymph nodes undergoing an immune response to the streptococcal group A-variant polysaccharide (Av-CHO).
Proline Oxidase Promotes Tumor Cell Survival in Hypoxic Tumor Microenvironments
Authors: Wei Liu, Kristine Glunde, Zaver M. Bhujwalla, Venu Raman, Anit Sharma, James M. Phang
Journal: Cancer Research (2012)

Abstract Proline is a readily released stress substrate that can be metabolized by proline oxidase (POX) to generate either reactive oxygen species (ROS) to induce apoptosis or autophagy or ATP during times of nutrient stress. However, the contribution of proline metabolism to tumorigenesis in hypoxic microenvironments has not been explored. In this study, we investigated the different functions of POX under hypoxia and glucose depletion. We found that hypoxia induced POX expression in cancer cells in vitro and that POX upregulation colocalized with hypoxic tissues in vivo. In addition, the combination of hypoxia and low glucose showed additive effects on POX expression. Similar to conditions of low glucose, hypoxia-mediated POX induction was dependent on AMP-activated protein kinase activation but was independent of HIF-1α and HIF-2α. Under low-glucose and combined low-glucose and hypoxic conditions, proline catabolized by POX was used preferentially for ATP production, whereas under hypoxia, POX mediated autophagic signaling for survival by generating ROS. Although the specific mechanism was different for hypoxia and glucose deprivation, POX consistently contributed to tumor cell survival under these conditions. Together, our findings offer new insights into the metabolic reprogramming of tumor cells present within a hostile microenvironment and suggest that proline metabolism is a potential target for cancer therapeutics. Cancer Res; 72(14); 3677–86. ©2012 AACR.
Combination of Polymorphisms From Genes Related to Estrogen Metabolism and Risk of Prostate Cancers: The Hidden Face of Estrogens
Authors: Olivier Cussenot, Abdel Rhamene Azzouzi, Nathalie Nicolaiew, Gaelle Fromont, Philippe Mangin, Luc Cormier, Georges Fournier, Antoine Valeri, Stephane Larre, Frederic Thibault, Jean-Pierre Giordanella, Michel Pouchard, Yan Zheng, Freddie C. Hamdy, Angela Cox, Geraldine Cancel-Tassin
Journal: Journal of Clinical Oncology (2007)

The association between common functional polymorphisms from the CYP17, CYP19, CYP1B1, and COMT genes involved in the estrogen metabolism and the risk of prostate carcinoma was evaluated.The study investigated 1,983 white French men (1,101 patients with prostate cancer and 882 healthy controls) aged between 40 and 98 years. The different alleles and genotypes were analyzed according to case-control status, aggressiveness pattern of the tumors, age at onset, and family history of cancers.The VV (high activity) genotype of the V432L polymorphism from CYP1B1 (odds ratio [OR] = 1.36; 95% CI, 1.03 to 1.79; P = .031), and the long allele (> 175 bp) of the TTTA repeat from CYP19 (OR, 1.26; 95% CI, 1.08 to 1.47; P = .003) were significantly associated with the risk of prostate cancer. An additive effect was observed when we combined the two at-risk alleles (OR = 1.63; 95% CI, 1.24 to 2.13; P < .001). The association was stronger for the CYP1B1 VV genotype (OR = 1.55; 95% CI, 1.13 to 2.13; P = .007) among the group of patients with highly aggressive disease. Stratification by age at onset showed that the associations of CYP1B1 and CYP19 variants were largely confined to the younger prostate cancer patients.This association between polymorphisms from genes related to estrogen metabolism and prostate cancer risk suggest new clinical considerations in the management of prostate cancer: the development of new prevention trials based on genetic profiling and the evaluation of specific inhibitors involving the estrogen pathways.
Bone Marrow Mesenchymal Stem Cells Provide an Alternate Pathway of Osteoclast Activation and Bone Destruction by Cancer Cells
Authors: Yasuyoshi Sohara, Hiroyuki Shimada, Cedric Minkin, Anat Erdreich-Epstein, Jan A. Nolta, Yves A. DeClerck
Journal: Cancer Research (2005)

Abstract The bone is the third most common site of cancer metastasis. To invade the bone, tumor cells produce osteoclast-activating factors that increase bone resorption by osteoclasts. Here we report that human neuroblastoma cells that form osteolytic lesions in vivo do not produce osteoclast-activating factors but rather stimulate osteoclast activity in the presence of human bone marrow mesenchymal stem cells. This alternative pathway of osteoclast activation involves a nonadhesive interaction between neuroblastoma cells and bone marrow mesenchymal stem cells. Stimulated bone marrow mesenchymal stem cells express markedly increased levels of interleukin-6, which is then responsible for osteoclast activation. This report describes a critical role of bone marrow mesenchymal stem cells in bone destruction in cancer.
Influence of Low High-Density Lipoprotein Cholesterol and Elevated Triglyceride on Coronary Heart Disease Events and Response to Simvastatin Therapy in 4S
Authors: Christie M. Ballantyne, Anders G. Olsson, Thomas J. Cook, Michele F. Mercuri, Terje R. Pedersen, John Kjekshus
Journal: Circulation (2001)

Background — Patients with low HDL cholesterol (HDL-C) and elevated triglyceride had an increased risk for coronary heart disease (CHD) events and received the greatest benefit with fibrate therapy in substudy analyses of the Helsinki Heart Study and the Bezafibrate Infarction Prevention Study. Methods and Results — In this post hoc analysis of the Scandinavian Simvastatin Survival Study, which enrolled patients with elevated LDL cholesterol (LDL-C) and CHD, subgroups defined by HDL-C and triglyceride quartiles were compared to examine the influence of HDL-C and triglyceride on CHD events and response to therapy. Patients in the lowest HDL-C (&lt;1.00 mmol/L [39 mg/dL]) and highest triglyceride (&gt;1.80 mmol/L [159 mg/dL]) quartiles (lipid triad; n=458) had increased proportions of other features of the metabolic syndrome (increased body mass index, hypertension, diabetes), men, prior myocardial infarction, prior revascularization, and β-blocker use than patients in the highest HDL-C (&gt;1.34 mmol/L [52 mg/dL]) and lowest triglyceride (&lt;1.11 mmol/L [98 mg/dL]) quartiles (isolated LDL-C elevation; n=545). The major coronary event rate was highest in lipid triad patients on placebo (35.9%), and this subgroup had the greatest event reduction (relative risk 0.48, 95% CI 0.33 to 0.69); a significant treatment-by-subgroup interaction ( P =0.03) indicated a greater treatment effect in the lipid triad subgroup than the isolated LDL-C elevation subgroup. Conclusions — Patients with elevated LDL-C, low HDL-C, and elevated triglycerides were more likely than patients with isolated LDL-C elevation to have other characteristics of the metabolic syndrome, had increased risk for CHD events on placebo, and received greater benefit with simvastatin therapy.
Antigenic Properties of a Nonreleaser Neoplasm Induced in the Mouse by Murine Sarcoma Virus
Authors: L. W. Law, R. C. Ting
Journal: JNCI Journal of the National Cancer Institute (1970)

Pseudotype virus-specific antigcnicity has been detected in a nonreleaser neoplasm, a hemangiosarcoma induced by MSV(MLV), the pseudotype virus of the murine sarcoma virus bearing the envelope of the Moloney leukemogenic virus; MLV was used as a “helper” virus in the rescue of this pseudotype virus. The neoplasm XM-1 was selected by passage through immunologically deficient syngeneic, BC3HF1 mice. Data from these experiments support the concept that virus-specific cell surface antigens, as detected by transplantation procedures, do exist on RNA virus-induced neoplastic cells, and that these antigens are distinct from antigens of the virus. Though not decisive, the evidence also favors the assumption of a direct relationship between viral genetic material (in the “defective” state) maintained in these neoplastic cells and the presence of tumor-specific transplantation antigens.
Angiopoietin-2 Interferes with Anti-VEGFR2–Induced Vessel Normalization and Survival Benefit in Mice Bearing Gliomas
Authors: Sung-Suk Chae, Walid S. Kamoun, Christian T. Farrar, Nathaniel D. Kirkpatrick, Elisabeth Niemeyer, Annemarie M.A. de Graaf, A. Gregory Sorensen, Lance L. Munn, Rakesh K. Jain, Dai Fukumura
Journal: Clinical Cancer Research (2010)

Abstract Purpose: In brain tumors, cerebral edema is a significant source of morbidity and mortality. Recent studies have shown that inhibition of vascular endothelial growth factor (VEGF) signaling induces transient vascular normalization and reduces cerebral edema, resulting in a modest survival benefit in glioblastoma patients. During anti-VEGF treatment, circulating levels of angiopoietin (Ang)-2 remained high after an initial minor reduction. It is not known, however, whether Ang-2 can modulate anti-VEGF treatment of glioblastoma. Here, we used an orthotopic glioma model to test the hypothesis that Ang-2 is an additional target for improving the efficacy of current anti-VEGF therapies in glioma patients. Experimental Design: To recapitulate high levels of Ang-2 in glioblastoma patients during anti-VEGF treatment, Ang-2 was ectopically expressed in U87 glioma cells. Animal survival and tumor growth were assessed to determine the effects of Ang-2 and anti–VEGF receptor 2 (VEGFR2) treatment. We also monitored morphologic and functional vascular changes using multiphoton laser scanning microscopy and immunohistochemistry. Results: Ectopic expression of Ang-2 had no effect on vascular permeability, tumor growth, or survival, although it resulted in higher vascular density, with dilated vessels and reduced mural cell coverage. On the other hand, when combined with anti-VEGFR2 treatment, Ang-2 destabilized vessels without affecting vessel regression and compromised the survival benefit of VEGFR2 inhibition by increasing vascular permeability. VEGFR2 inhibition normalized tumor vasculature whereas ectopic expression of Ang-2 diminished the beneficial effects of VEGFR2 blockade by inhibiting vessel normalization. Conclusion: Cancer treatment regimens combining anti-VEGF and anti-Ang-2 agents may be an effective strategy to improve the efficacy of current anti-VEGF therapies. Clin Cancer Res; 16(14); 3618–27. ©2010 AACR.
Respiration after phrenicotomy and hydrocortisone treatment in anaesthetized rats
Authors: J Nachazel, F Palecek
Journal: European Respiratory Journal (1993)

The study was designed to determine the extent to which respiratory muscle wasting, resulting from corticosteroid-induced atrophy, may affect respiration in normal rats and in rats with denervated diaphragm. Twenty four male Wistar rats were divided into four groups: 1) controls with sham operation (SX) and vehicle injections: 2) SX with eight hydrocortisone (HC) injections (60 mg.kg-1.day-1 i.m.); 3) phrenicotomized (PX), injected with vehicle; 4) PX and HC-treated. HC treatment was started on the thirteenth day after surgery. Under urethane anaesthesia, tidal volume, respiratory rate, arterial carbon dioxide tension (PaCO2) and occlusion pressure were measured at rest and after 5 min of stimulated-breathing induced by added dead space 22nd day after surgery. All HC-treated animals decreased body weight by 32% compared to untreated rats. The diaphragm weight was reduced in PX rats by 29%, and after HC by 44%, while in PX rats with HC treatment diaphragm weight decreased by only 21%. PX rats (HC-untreated) had the lowest minute ventilation and occlusion pressure. There was no difference in ventilation between control and both HC-treated groups at rest. However, ventilation in PX and HC-treated rats did not increase upon stimulation, and the occlusion pressure increased significantly only in the HC-untreated animals. We conclude that in the rat, HC treatment did not affect resting ventilation, but it impaired ventilation performance, during increased demand, in animals handicapped by diaphragm denervation.
Cardiovascular Disease in Diabetes.
Authors: G N BEATCH
Journal: Cardiovascular Research (1993)

Journal Article Cardiovascular Disease in Diabetes. Get access G N BEATCH G N BEATCH Ontario, Canada Edited by M Nagano, S Mochizuki, and N S Dhalla. (Pp 388; £76.25.) Kluwer, 1992. ISBN 0-792-315545. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 8, August 1993, Page 1554, https://doi.org/10.1093/cvr/27.8.1554 Published: 01 August 1993
Impact of Baseline Corticosteroids on Survival and Steroid Androgens in Metastatic Castration-resistant Prostate Cancer: Exploratory Analysis from COU-AA-301
Authors: Bruce Montgomery, Thian Kheoh, Arturo Molina, Jinhui Li, Joaquim Bellmunt, NamPhuong Tran, Yohann Loriot, Eleni Efstathiou, Charles J. Ryan, Howard I. Scher, Johann S. de Bono
Journal: European Urology (2014)
Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome
Authors: Russell J Ferland, Wafaa Eyaid, Randall V Collura, Laura D Tully, R Sean Hill, Doha Al-Nouri, Ahmed Al-Rumayyan, Meral Topcu, Generoso Gascon, Adria Bodell, Yin Yao Shugart, Maryellen Ruvolo, Christopher A Walsh
Journal: Nature Genetics (2004)
Obligatory Role of Cyclic Adenosine Monophosphate Response Element in Cyclooxygenase-2 Promoter Induction and Feedback Regulation by Inflammatory Mediators
Authors: Karsten Schroer, Ying Zhu, Michael A. Saunders, Wu-Guo Deng, Xiao-Ming Xu, Jutta Meyer-Kirchrath, Kenneth K. Wu
Journal: Circulation (2002)

Cyclooxygenase-2 (COX-2) plays a key role in human inflammatory disorders such as vascular inflammation. COX-2 promoter activity is induced by proinflammatory mediators, but the role of cyclic adenosine monophosphate response element (CRE) in promoter stimulation remains unclear.Transient transfection of a 0.9-kb COX-2 promoter fragment bearing CRE mutation abrogated COX-2 promoter activity induced by proinflammatory mediators in human endothelial cells and fibroblasts. Dual mutations of CRE and an upstream CCAAT/enhancer binding protein (C/EBP) site did not have an additional effect. Binding of CREB-2, ATF-2, USF-2, and c-Jun transactivators to a wild-type and CRE-mutated oligonucleotide was analyzed by a novel DNA-binding assay. CREB-2 and ATF-2 in nuclear extracts of unstimulated endothelial cells bound to CRE, whereas USF-2 and c-Jun or c-Fos bound to non-CRE sites. CREB-2 and c-Fos binding was increased by phorbol 12-myristate 13-acetate but not tumor necrosis factor-alpha. The binding assay and chromatin immunoprecipitation revealed binding of P300 coactivator to the COX-2 promoter region.CRE plays an obligatory role in COX-2 promoter activation by diverse stimuli. CREB-2 and ATF-2 bound to CRE serve as an anchor for P300 interaction with upstream transactivators and downstream transcription machinery.