tbuckley/cabot-search huggingface dataset:
Effects of a Mediterranean-Style Diet on Cardiovascular Risk Factors
Authors: Ramon Estruch
Journal: Annals of Internal Medicine (2006)

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: The Mediterranean diet has been shown to have beneficial effects on cardiovascular risk factors. Objective: To compare the short-term effects of 2 Mediterranean diets versus those of a low-fat diet on intermediate markers of cardiovascular risk. Design: Substudy of a multicenter, randomized, primary prevention trial of cardiovascular disease (Prevención con Dieta Mediterránea [PREDIMED] Study). Setting: Primary care centers affiliated with 10 teaching hospitals. Participants: 772 asymptomatic persons 55 to 80 years of age at high cardiovascular risk who were recruited from October 2003 to March 2004. Interventions: Participants were assigned to a low-fat diet (n = 257) or to 1 of 2 Mediterranean diets. Those allocated to Mediterranean diets received nutritional education and either free virgin olive oil, 1 liter per week (n = 257), or free nuts, 30 g/d (n = 258). The authors evaluated outcome changes at 3 months. Measurements: Body weight, blood pressure, lipid profile, glucose levels, and inflammatory molecules. Results: The completion rate was 99.6%. Compared with the low-fat diet, the 2 Mediterranean diets produced beneficial changes in most outcomes. Compared with the low-fat diet, the mean changes in the Mediterranean diet with olive oil group and the Mediterranean diet with nuts group were −0.39 mmol/L (95% CI, −0.70 to − 0.07 mmol/L) and − 0.30 mmol/L (CI, −0.58 to − 0.01 mmol/L), respectively, for plasma glucose levels; −5.9 mm Hg (CI, −8.7 to −3.1 mm Hg) and − 7.1 mm Hg (CI, −10.0 to −4.1 mm Hg), respectively, for systolic blood pressure; and −0.38 (CI, −0.55 to − 0.22) and − 0.26 (CI, −0.42 to −0.10), respectively, for the cholesterol–high-density lipoprotein cholesterol ratio. The Mediterranean diet with olive oil reduced C-reactive protein levels by 0.54 mg/L (CI, 1.04 to 0.03 mg/L) compared with the low-fat diet. Limitations: This short-term study did not focus on clinical outcomes. Nutritional education about low-fat diet was less intense than education about Mediterranean diets. Conclusion: Compared with a low-fat diet, Mediterranean diets supplemented with olive oil or nuts have beneficial effects on cardiovascular risk factors. *For a list of additional PREDIMED Study Investigators, see the Appendix.
Acute Effects of Ethanol Ingestion on the Response to Submaximal and Maximal Exercise in Man
Authors: GUNNAR BLOMQVIST, BENGT SALTIN, JERE H. MITCHELL, George F. Vastagh
Journal: Circulation (1970)

The acute effects of ingestion of ethanol on the response to submaximal and maximal exercise were studied by noninvasive technics in a group of eight healthy men, ages 21 to 33 (series I). Cardiac output (dye-dilution technic) and intra-arterial pressures were measured in a separate series of experiments in a subgroup of four subjects (series II). Mean concentration of ethanol in the blood at the end of the experiment was 156 mg/100 ml in series I and 125 mg/100 ml in series II. Heart rates at rest and during submaximal exercise were higher after ingestion of ethanol, but there was no effect on stroke volume. After ingestion of ethanol cardiac output at rest and during submaximal exercise increased, and total A-V difference and total peripheral resistance decreased. The circulatory response to maximal work was not affected by ethanol. Maximal oxygen uptake did not change. Pulmonary ventilation was not altered during submaximal exercise but was reduced during maximal work. These findings are in agreement with data from animal experiments suggesting that ethanol in blood concentrations below 200 mg/100 ml has no significant depressive effect on performance of the normal heart.
THE ACTIVATING, TRANSFORMING, AND CARCINOGENIC EFFECTS OF THE RABBIT PAPILLOMA VIRUS (SHOPE) UPON IMPLANTED TAR TUMORS
Authors: Peyton Rous, John G. Kidd
Journal: The Journal of Experimental Medicine (1940)

The effects of the rabbit papilloma virus upon tar tumor tissue are widely various, as the present paper and previous ones attest. It enables some of the benign tar tumors of domestic rabbits (papillomas, carcinomatoids) to establish themselves after implantation,-which they are unable to do under ordinary circumstances, being dependent upon favoring factors; and it may drive them to active proliferation without altering their morphology. Some growths it fails to influence and some it converts into virus papillomas. Often, however, it brings about cytological changes which are indicative of a combination of its influence with that of the undetermined factor motivating the original tumor. The resulting neoplasm exhibits a blend of characteristics. The virus makes some benign tar tumors become cancerous forthwith, the malignancy developing without intermediate virus papillomatosis. It can be readily imposed upon some of the squamous cell carcinomas which tar elicits in its natural host, the cottontail rabbit, and it may drive such tumors to proliferate faster, or alter them morphologically, or do both. Its stimulating effect is especially pronounced in the case of those tar cancers that are slow-growing. Since the virus can influence tar cancers markedly, one can scarcely suppose it to be devoid of effect upon the cancers of the same type which derive from the papillomas it has itself engendered. Other implications of the work are discussed.
A 25 year single centre experience in 128 patients with primary sclerosing cholangitis
Authors: M. H. Chapman, S. Bannoo, G. Webster, G. Johnson, A. R. Hatfield, S. P. Pereria, G. Johnson
Journal: Gut (2011)

<h3>Introduction</h3> Dominant biliary strictures (DS) occur commonly in patients with primary sclerosing cholangitis (PSC), who have an increased risk of developing cholangiocarcinoma (CCA). The natural history and optimal management of dominant strictures remains controversial with most reports suggesting that endoscopic interventions improve outcome. <h3>Methods</h3> The authors describe a 25 year experience of endoscopic retrograde cholangiopancreatography (ERCP) in patients with PSC at a single tertiary referral centre in London. Patients were identified through case note review, endoscopy and pathology database searches and through a specific PSC database. <h3>Results</h3> During a mean follow-up of 6 years (0.1–23.6 years), 128 patients with PSC (81 M, 47 F; median age 49 years) had a median of 2 ERCPs (range 1–24). 70 patients with dominant biliary strictures had a median of 3 (range 0–34) interventions, compared to 1 (0–7) in the 58 without dominant strictures. Endoscopic interventions included: (1) stenting alone (51%), (2) dilatation alone (19%) or (3) dilatation and stenting (16%), while 14% had no or failed interventions, most of whom required percutaneous transhepatic drainage. There were no procedure-related deaths. The survival of those with dominant strictures was worse than those without, even after exclusion of those who developed CCA. Use of ursodeoxycholic acid was not significantly different between groups. CCA developed in 20/128 patients (16%), only in those with dominant strictures (20 of 70, 29%, compared to 0 of 58). Jaundice was the presenting feature in 15 (75%) of those with CCA, which developed a median of 3 years (0–21 years) after the diagnosis of PSC, with 8/20 (40%) presenting within the first year. Mean time from diagnosis of CCA to death was 7 months (1–23 months). <h3>Conclusion</h3> Repeated endoscopic therapy in patients with PSC appears to be safe. However, this data highlights the poor prognosis in the subgroup with dominant strictures, even after exclusion of those who developed CCA. In this series, CCA only occurred in patients with dominant bile duct strictures.
ATF4 Regulates MYC-Mediated Neuroblastoma Cell Death upon Glutamine Deprivation
Authors: Guoliang Qing, Bo Li, Annette Vu, Nicolas Skuli, Zandra E. Walton, Xueyuan Liu, Patrick A. Mayes, David R. Wise, Craig B. Thompson, John M. Maris, Michael D. Hogarty, M. Celeste Simon
Journal: Cancer Cell (2012)
Evidence for Replicative Repair of DNA Double-Strand Breaks Leading to Oncogenic Translocation and Gene Amplification
Authors: Michael J. Difilippantonio, Simone Petersen, Hua Tang Chen, Roger Johnson, Maria Jasin, Roland Kanaar, Thomas Ried, André Nussenzweig
Journal: The Journal of Experimental Medicine (2002)

Nonreciprocal translocations and gene amplifications are commonly found in human tumors. Although little is known about the mechanisms leading to such aberrations, tissue culture models predict that they can arise from DNA breakage, followed by cycles of chromatid fusion, asymmetric mitotic breakage, and replication. Mice deficient in both a nonhomologous end joining (NHEJ) DNA repair protein and the p53 tumor suppressor develop lymphomas at an early age harboring amplification of an IgH/c-myc fusion. Here we report that these chromosomal rearrangements are initiated by a recombination activating gene (RAG)-induced DNA cleavage. Subsequent DNA repair events juxtaposing IgH and c-myc are mediated by a break-induced replication pathway. Cycles of breakage-fusion-bridge result in amplification of IgH/c-myc while chromosome stabilization occurs through telomere capture. Thus, mice deficient in NHEJ provide excellent models to study the etiology of unbalanced translocations and amplification events during tumorigenesis.
Intravenous streptokinase for acute myocardial infarction. Effects on global and regional systolic function.
Authors: G V Martin, F H Sheehan, M Stadius, C Maynard, K B Davis, J L Ritchie, J W Kennedy
Journal: Circulation (1988)

The Western Washington Intravenous Streptokinase Trial randomized 368 patients with acute myocardial infarction to receive either intravenous streptokinase or standard therapy. The ventriculograms and coronary angiograms obtained in 170 patients 10.4 +/- 7.4 days after infarction were analyzed to evaluate the effects of thrombolytic therapy on global and regional systolic function. Streptokinase treatment resulted in a higher patency rate of the infarct-related artery (68.5%) than did standard therapy (44.8%) (p = 0.003). Ejection fraction was higher in streptokinase-treated patients (54% vs. 51%, p = 0.056), and the difference was most marked in patients with anterior myocardial infarction (53% vs. 44%, p = 0.03). Regional wall motion was measured by the centerline method and expressed in mean +/- SD motion in 52 normal subjects. There was a trend toward better function of the infarct zone in streptokinase-treated patients (SD, -2.48 vs. -2.70, p = 0.24). Additionally, streptokinase-treated patients had significantly better wall motion of noninfarct areas (SD, 0.36 vs. -0.08, p = 0.02). Treatment effects on function of noninfarct regions were most apparent in the subset of patients with multivessel disease. Thus, intravenous streptokinase preserves left ventricular function in patients with acute myocardial infarction. This benefit includes favorable effects on the function of regions remote from the site of infarction.
Novel Venom Proteins Produced by Differential Domain-Expression Strategies in Beaded Lizards and Gila Monsters (genus Heloderma)
Authors: B. G. Fry, K. Roelants, K. Winter, W. C. Hodgson, L. Griesman, H. F. Kwok, D. Scanlon, J. Karas, C. Shaw, L. Wong, J. A. Norman
Journal: Molecular Biology and Evolution (2009)

The origin and evolution of venom proteins in helodermatid lizards were investigated by multidisciplinary techniques. Our analyses elucidated novel toxin types resultant from three unique domain-expression processes: 1) The first full-length sequences of lethal toxin isoforms (helofensins) revealed this toxin type to be constructed by an ancestral monodomain, monoproduct gene (beta-defensin) that underwent three tandem domain duplications to encode a tetradomain, monoproduct with a possible novel protein fold; 2) an ancestral monodomain gene (encoding a natriuretic peptide) was medially extended to become a pentadomain, pentaproduct through the additional encoding of four tandemly repeated proline-rich peptides (helokinestatins), with the five discrete peptides liberated from each other by posttranslational proteolysis; and 3) an ancestral multidomain, multiproduct gene belonging to the vasoactive intestinal peptide (VIP)/glucagon family being mutated to encode for a monodomain, monoproduct (exendins) followed by duplication and diversification into two variant classes (exendins 1 and 2 and exendins 3 and 4). Bioactivity characterization of exendin and helokinestatin elucidated variable cardioactivity between isoforms within each class. These results highlight the importance of utilizing evolutionary-based search strategies for biodiscovery and the virtually unexplored potential of lizard venoms in drug design and discovery.
Radiological progression of hip osteoarthritis: definition, risk factors and correlations with clinical status.
Authors: M Dougados, A Gueguen, M Nguyen, L Berdah, M Lequesne, B Mazieres, E Vignon
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVES: To determine a cut off value for changes in radiological joint space width that allowed definition of radiological progression of hip osteoarthritis not related to measurement method errors and, thereafter, to determine factors predictive of radiological progression of hip osteoarthritis and to evaluate the correlations between clinical and radiological parameters. METHODS: A prospective, longitudinal (one year duration), multicentre study was made of patients with osteoarthritis of the hip (American College of Rheumatology criteria). Data on clinical activity (pain, functional impairment), demographic data (age, gender, body mass index), and femoral head migration (superolateral, superomedial, concentric) were collected when the patient entered the study; radiological grade (joint space width in millimetres at the narrowest point using a 0.1 mm graduated magnifying glass, evaluated by a single observer unaware of the chronology of the films) was recorded at the patient9s entry to the study and after one year. RESULTS: Analysis of the means of the differences between two analyses performed by a single observer of 30 pairs of radiographs (one performed after an interval of one year) (0.06 (SD 0.23)) suggested that a change of more than 0.56 mm (2 SD) after a one year follow up could define progression of osteoarthritis of the hip. Of the 508 patients recruited, 461 (91%) completed the one year follow up and radiological progression was observed in 102 (22%). The factors predictive of radiological progression that were identified in the multivariate analysis were: radiological joint space width at entry &lt; or = 2 mm, superolateral migration of the femoral head, female gender, Lequesne9s functional index &gt; 10, age at entry &gt; 65 years (odds ratios 2.11, 4.25, 2.51, 2.66, 1.90, respectively). The level of clinical parameters (pain, functional impairment) and the amount of symptomatic treatment required (non-steroidal anti-inflammatory drugs and analgesic intake) accounted for 20% (p &lt; 0.0001) of the variability of the changes in radiological joint space width over the one year study period. CONCLUSION: These data suggest that radiological progression of hip osteoarthritis could be defined by a change in joint space width of at least 0.6 mm after a one year follow up period, is correlated with the changes in clinical status of the patients, and is related not only to demographic data (age, gender), but also to some specific characteristics of osteoarthritis (localisation, radiological severity, clinical activity).
Schedule-dependent enhancement of the cytotoxicity of fluoropyrimidines to human carcinoma cells in the presence of folinic acid.
Authors: Moran Rg, Scanlon Kl
Journal: Cancer Research (1991)

Abstract  Previous studies from this laboratory indicated that the cytotoxic effects of the fluoropyrimidines on mouse leukemic cells are substantially augmented by folinic acid but that these effects are underestimated in growth inhibition experiments. These results have now been extended to two human tumor cell lines, the WiDr colorectal and T-24 bladder carcinoma cells. In both cell lines, the presence of folinic acid in the medium substantially enhanced the cytotoxicity of a 72-h exposure to either 5-fluorouracil (FUra) or 5-fluoro-2′-deoxyuridine. Folinic acid concentration-response curves for enhancement of the cytotoxicity of FUra to WiDr cells were broad but indicated that response was not maximal until at least 10 µm. Likewise, increased length of exposure to 10 µm folinic acid continuously enhanced the cytotoxicity of a 72-h treatment with FUra, but substantial enhancement was observed even after a 2-h exposure to folinate, and there was a diminished increment of cytotoxicity after 24-h exposure to folinic acid. Surprisingly, folinic acid augmentation of the cytotoxicity of a brief exposure to FUra (4 h) was minimal but enhancement of FUra cytotoxicity became much more pronounced with intervals of exposure to FUra of ≥24 h. If these results can be mimicked  in vivo  without undue host toxicity, our experiments suggest that a substantial improvement in the therapeutic activity of FUra plus folinate would result from prolonged exposure to both agents.
A new synthetic protein, TAT-RH, inhibits tumor growth through the regulation of NFκB activity
Authors: Daniela Sorriento, Alfonso Campanile, Gaetano Santulli, Eleonora Leggiero, Lucio Pastore, Bruno Trimarco, Guido Iaccarino
Journal: Molecular Cancer (2009)

Abstract Background Based on its role in angiogenesis and apoptosis, the inhibition of NFκB activity is considered an effective treatment for cancer, hampered by the lack of selective and safe inhibitors. We recently demonstrated that the RH domain of GRK5 (GRK5-RH) inhibits NFκB, thus we evaluated its effects on cancer growth. Methods The role of GRK5-RH on tumor growth was assessed in a human cancer cell line (KAT-4). RH overexpression was induced by adenovirus mediated gene transfer; alternatively we administered a synthetic protein reproducing the RH domain of GRK5 (TAT-RH), actively transported into the cells. Results In vitro , adenovirus mediated GRK5-RH overexpression (AdGRK5-NT) in human tumor cells (KAT-4) induces IκB accumulation and inhibits NFκB transcriptional activity leading to apoptotic events. In BALB/c nude mice harboring KAT-4 induced neoplasias, intra-tumor delivery of AdGRK5-NT reduces in a dose-dependent fashion tumor growth, with the highest doses completely inhibiting it. This phenomenon is paralleled by a decrease of NFκB activity, an increase of IκB levels and apoptotic events. To move towards a pharmacological setup, we synthesized the TAT-RH protein. In cultured KAT-4 cells, different dosages of TAT-RH reduced cell survival and increased apoptosis. In BALB/c mice, the anti-proliferative effects of TAT-RH appear to be dose-dependent and highest dose completely inhibits tumor growth. Conclusion Our data suggest that GRK5-RH inhibition of NFκB is a novel and effective anti-tumoral strategy and TAT-RH could be an useful tool in the fighting of cancer.
Lipid Composition and Metabolism of Thromboatherosclerotic Lesions Produced by Continued Endothelial Damage in Normal Rabbits
Authors: ALLAN J. DAY, FRANK P. BELL, SEAN MOORE, ROBERT FRIEDMAN
Journal: Circulation Research (1974)

Thromboatherosclerotic and fibrous lesions were produced by endothelial damage with polyethylene catheters inserted into the aortas in rabbits on a normal diet. Two weeks after insertion of the catheters, the concentration of both free cholesterol and cholesteryl ester in the thromboatherosclerotic lesions was significantly greater than that in the adjacent normal intima. A further increase in the concentration of free cholesterol and particularly of cholesteryl ester occurred during the remainder of the 4-month study period. Gas-liquid chromatography indicated that the raised thromboatherosclerotic lesions contained more cholesteryl oleate and less cholesteryl linoleate than did either the normal intima or the fibrous lesions. The incorporation of [1 -14 C] oleic acid into combined lipid in the aortas incubated in vitro showed that, by 2 weeks, two to three times more oleic acid had been incorporated into cholesteryl ester in the thromboatherosclerotic raised lesions than in the normal intima. A similar increase was demonstrated at 2 and 4 months. When [ 32 P] phosphate was used as a precursor, incorporation into lecithin was higher and incorporation into phosphatidyl inositol was lower in the raised lesions than they were in the normal intima. Fibrous lesions did not differ significantly from the adjacent normal intima in their incorporation of either of these precursors into lipid. Therefore, the accumulation of cholesteryl ester in the thromboatherosclerotic lesions resulted in part from synthesis in the arterial wall, which was stimulated by the prominent platelet components of the lesions.
Aggregations of Lymphoid Cells in the Airways of Nonsmokers, Smokers, and Subjects with Asthma
Authors: John G. Elliot, Cathryn M. Jensen, Slavko Mutavdzic, Jasmine P. Lamb, Neil G. Carroll, Alan L. James
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Persistent airway inflammation is present in cases with asthma and in smokers with airflow obstruction. Isolated aggregations of lymphoid cells (IALC) may be sites of localized inflammatory cell activation. Their distribution and characteristics in cartilaginous airways were assessed in postmortem tissue from nonsmokers (n=10), smokers (n=9), and cases of nonfatal (n=10) and fatal asthma (n=10). IALC were present in 70-100% of cases, were more often in proximal than distal airways, and 80% were confined to the outer airway wall. IALC with area greater than 0.1 mm2 were more frequent in both asthma groups (p<0.001). Airways with IALC had increased airway dimensions and greater numbers of eosinophils and lymphomononuclear cells. Within IALC, T and B lymphocytes were segregated and comprised more than 90% of all cells. Proliferating, apoptotic, and antigen-presenting cells (Rel B+ and HLA-DR+) were less than 5%, 30-40%, and less than 1% of all cells, respectively, and were similar in each case group. Vascular structures were increased (p < 0.01) in cases of fatal asthma. These findings show that, even in nonsmoking cases and cases without asthma, IALC are common, show cellular organization, and are associated with airway wall inflammation and remodeling. It remains to be determined if IALC contribute to or result from persistent airway inflammation in asthma.
Gli Proteins Up-Regulate the Expression of Basonuclin in Basal Cell Carcinoma
Authors: Chunhua Cui, Thomas Elsam, Qinjie Tian, John T. Seykora, Marina Grachtchouk, Andrzej Dlugosz, Hung Tseng
Journal: Cancer Research (2004)

Abstract Tumorigenesis is frequently accompanied by enhanced rRNA transcription, but the signaling mechanisms responsible for such enhancement remain unclear. Here, we report evidence suggesting a novel link between deregulated Hedgehog signaling and the augmented rRNA transcription in cancer. Aberrant activation of the Hedgehog pathway in keratinocytes is a hallmark of basal cell carcinoma (BCC), the most common cancer in light-skinned individuals. We show that Gli proteins, downstream effectors of the Hedgehog pathway, increase expression of a novel rRNA gene (rDNA) transcription factor, basonuclin, whose expression is markedly elevated in BCCs. The promoter of the human basonuclin gene contains a Gli-binding site, which is required for Gli protein binding and transcriptional activation. We show also that the level of 47S pre-rRNA is much higher in BCCs than in normal epidermis, suggesting an accelerated rRNA transcription in the neoplastic cells. Within BCC, those cells expressing the highest level of basonuclin also exhibit the greatest increase in 47S pre-rRNA, consistent with a role for basonuclin in increasing rRNA transcription in these cells. Our data suggest that Hedgehog-Gli pathway enhances rRNA transcription in BCC by increasing basonuclin gene expression.