tbuckley/cabot-search huggingface dataset:
Acromegaly and Cardiovascular Disorders
Authors: WILLIAM L. MCGUFFIN
Journal: Annals of Internal Medicine (1974)

In a prospective study of cardiovascular findings in 57 patients with acromegaly, hypertension was found in 13. As a group, the hypertensives were older, had their acromegaly longer, and had higher plasma growth hormone concentrations. Typically, the hypertension was mild, uncomplicated, and responsive to drugs. Irrespective of blood pressure, nine patients had symptomatic heart disease, including four with arrhythmias, of whom three had hyperthyroidism. Seven of the nine patients had congestive heart failure, including two with coronary heart disease, two with cardiomyopathy, and two with arrhythmias. Cardiomegaly, although uniformly present at necropsy, was detected clinically only in patients with hypertension or congestive heart failure. In this series we were unable to measure the incidence or prevalence of cardiac disease in acromegaly, to detect a characteristic form of heart disease in acromegaly, or to define a clear relation between cardiac disease and the plasma growth hormone concentration.
Papillary Necrosis in Rats Caused by Aspirin and Aspirin-containing Mixtures
Authors: R. S. Nanra, P. Kincaid-Smith
Journal: BMJ (1970)

Nearly half the rats gavage-fed with aspirin and aspirin-containing mixtures developed papillary necrosis in 20 weeks. This incidence is similar to that found in rats on A.P.C. mixtures with high and low concentrations of <i>p</i>-chloracetanilide, an impurity of phenacetin. Aspirin alone produced necrosis in 7 out of 19 rats (36·8%) whereas phenacetin in the same dose had failed to cause any renal damage over six to nine months. If these results also apply to man they suggest that aspirin and not phenacetin may be the major factor in analgesic nephropathy in patients taking A.P.C. mixtures. An augmented clearance of aspirin appeared to afford some protection to the medulla, and it is suggested that this observation may have important clinical and epidemiological applications.
A Prospective Study of <i>Trans</i> Fatty Acids in Erythrocytes and Risk of Coronary Heart Disease
Authors: Qi Sun, Jing Ma, Hannia Campos, Susan E. Hankinson, JoAnn E. Manson, Meir J. Stampfer, Kathryn M. Rexrode, Walter C. Willett, Frank B. Hu
Journal: Circulation (2007)

High consumption of trans fat has been linked to the risk of coronary heart disease (CHD). We assessed the hypothesis that higher trans fatty acid contents in erythrocytes were associated with an elevated risk of CHD in a nested case-control study among US women.Blood samples were collected from 32,826 participants of the Nurses' Health Study from 1989 to 1990. During 6 years of follow-up, 166 incident cases of CHD were ascertained and matched with 327 controls. Total trans fatty acid content in erythrocytes was significantly correlated with dietary intake of trans fat (correlation coefficient=0.44, P<0.01) and was associated with increased plasma low-density lipoprotein cholesterol (P for trend =0.06), decreased plasma high-density lipoprotein cholesterol concentrations (P for trend <0.01), and increased plasma low-density lipoprotein to high-density lipoprotein ratio (P for trend <0.01). After adjustment for age, smoking status, and other dietary and lifestyle cardiovascular risk factors, higher total trans fatty acid content in erythrocytes was associated with an elevated risk of CHD. The multivariable relative risks (95% confidence intervals) of CHD from the lowest to highest quartiles of total trans fatty acid content in erythrocytes were 1.0 (reference), 1.6 (0.7 to 3.6), 1.6 (0.7 to 3.4), and 3.3 (1.5 to 7.2) (P for trend <0.01). The corresponding relative risks were 1.0, 1.1, 1.3, and 3.1 (P for trend <0.01) for a total of 18:1 trans isomers and 1.0, 1.5, 2.5, and 2.8 (P for trend <0.01) for a total of 18:2 trans isomers.These biomarker data provide further evidence that high trans fat consumption remains a significant risk factor for CHD after adjustment for covariates.
Goodbye PubMed, hello raw data
Authors: F. Godlee
Journal: BMJ (2011)

This time last year the H1N1 influenza pandemic was burning itself out, having caused, thankfully, far less sickness and death than predicted. Now this year’s seasonal flu epidemic is doing its rounds in the northern hemisphere (doi:10.1136/bmj.d203, doi:10.1136/bmj.d190). The UK’s problems with uptake and availability of the flu vaccine seem to have been sorted out, but what interests me is this year’s low key approach to antivirals.

You will remember that neuraminidase inhibitors were promoted by WHO as a key part of influenza prevention and treatment, and that oseltamivir was stockpiled at vast expense by most governments around the world. The drug was made widely …
Pharmacological possibilities for protection against myocardial reperfusion injury
Authors: Q Wang
Journal: Cardiovascular Research (2002)

Reperfusion through thrombolysis or percutananeous coronary angioplasty is standard treatment in impending acute myocardial infarction. Although restoration of blood flow to the jeopardised myocardial area is a perquisite for myocardial salvage, reperfusion itself may lead to accelerated and additional myocardial injury beyond that generated by ischemia alone. This is referred to as the "reperfusion injury". Since the reperfusion injury is initiated by the treatment of myocardial infarction, it is of importance to limit the extent of the injury. Several studies aimed at preventing reperfusion injury by means of pharmacological agents have therefore been conducted. The design of such studies is crucial for the results. Factors of importance are the timing of drug administration, animal species used, the degree of collateral flow and the duration of ischemia. A variety of pharmacological compounds have been investigated in different experimental models of myocardial ischemia and reperfusion. These include oxygen free radical scavengers, antioxidants, calcium channel blockers, inhibitors of neutrophils, nitric oxide, adenosine-related agents, inhibitors of the renin-angiotensin system, endothelin receptor antagonists, Na+/H+ exchange inhibitors, and anti-apoptotic agents. All these groups of pharmacological agents have been demonstrated to protect from reperfusion injury determined as limitation of infarct size, improved myocardial and endothelial function, and reduced incidence of arrhythmias. The mechanism behind the protective effect may differ between different groups of compounds, but some compounds may exert cardioprotection via common pathways. Such a pathway may be via maintained bioavailability of nitric oxide.
DNMT3B Overexpression by Deregulation of FOXO3a-Mediated Transcription Repression and MDM2 Overexpression in Lung Cancer
Authors: Yi-Chieh Yang, Yen-An Tang, Jiunn-Min Shieh, Ruo-Kai Lin, Han-Shui Hsu, Yi-Ching Wang
Journal: Journal of Thoracic Oncology (2014)
Two Cases of a Halfpenny in the OEsophagus
Authors: F. Johnston, C. T. Holland
Journal: BMJ (1896)

rI LJORAL 1i677 eome very curious effects on the skin.There have been several authentic cases reported, some of which I have myself seen.It is not quite certain, however, that this effect is an unmixed one.For in every case the affected skin has been in contact with other things than the rays, as, for instance, with platinocyanides and other substances used in preparing the screens.It has also been noted that those who have done most fluorescent work are the most affected.So until all other possible causes can be eliminated, it would be rash to draw conclusions.Writing in Nature, one observer records his ex- perience as follows:
Alpha-2 Globulin "Spike" in Renal Carcinoma
Authors: PETER MCPHEDRAN
Journal: Annals of Internal Medicine (1972)

A 44-year-old man was found to have a renal carcinoma after 8 months of constitutional symptoms. Initial study showed a puzzling array of laboratory abnormalities, including a prominent alpha-2 globulin "spike" on serum protein electrophoresis. Since the patient had plasmacytosis of the bone marrow, the diagnosis of multiple myeloma was considered but was discarded when the globulin proved to be haptoglobin. This case serves as a reminder of the propensity of early renal carcinoma to produce constitutional symptoms and of the variety of proteins that may produce alpha-2 peaks on electrophoresis.
Gastrointestinal Blood Loss and Anemia in Runners
Authors: JAMES G. STEWART
Journal: Annals of Internal Medicine (1984)

Iron deficiency, with or without anemia, occurs commonly in long-distance runners, but the cause is unknown. The recent development of a simple quantitative assay for fecal hemoglobin, HemoQuant, allowed us to study whether gastrointestinal bleeding occurs in runners. Blood and stool samples were collected from 24 runners before and after a race of 10 to 42.2 km and from age- and sex-matched, nonrunning controls. The mean blood hemoglobin level and hematocrit were significantly lower in runners than in controls. Serum ferritin levels were below normal in 4 runners but in no controls. Fecal hemoglobin levels increased in 20 of 24 runners (p < 0.01) after a race. Mean fecal hemoglobin level was 1.08 mg/g (range, 0.11 to 2.36) in controls and 0.99 mg/g (0.18 to 2.41) in runners before a race, but peaked at 3.96 mg/g (0.37 to 43.20) after a race. Competitive long-distance running induces gastrointestinal blood loss and may contribute to iron deficiency.
Measurement of δ-Aminolevulinic Acid Synthetase Activity in Human Erythroblasts
Authors: Yosuke Aoki, Gumpei Urata, Osamu Wada, Fumimaro Takaku
Journal: Journal of Clinical Investigation (1974)

A new, specific, and simple method for the determination of delta-aminolevulinic acid (ALA) synthetase activity in human bone marrow cells has been developed. ALA synthetase of erythroblasts was partially purified so as to permit the use of [(14)C]succinyl-CoA as a substrate for this enzyme. In this enzyme preparation there were negligible activities of succinyl-CoA hydrolase, alpha-ketoglutarate dehydrogenase, and succinyl-CoA synthetase and there was no activity of ALA dehydrase. The ALA formed from [(14)C]succinyl-CoA has been isolated by column chromatography. Radioactivity in the eluate from the column has been proved by paper chromatography to be exclusively that of [(14)C]ALA. The entire assay can be completed within 4 h, and [(14)C]succinyl-CoA was incorporated into [(14)C]ALA on the order of several percent. Moderate to marked decreases of ALA synthetase activity have been demonstrated in the erythroblasts of all cases of sideroblastic anemia. In the cases of iron deficiency anemia, on the other hand, normal or slightly elevated activity has been obtained.
Safe, Long-term Hepatic Expression of Anti-HCV shRNA in a Nonhuman Primate Model
Authors: David A Suhy, Shih-Chu Kao, Tin Mao, Laurence Whiteley, Hubert Denise, Bernard Souberbielle, Andrew D Burdick, Kyle Hayes, J Fraser Wright, Helen Lavender, Peter Roelvink, Alexander Kolykhalov, Kevin Brady, Sterghios A Moschos, Bernd Hauck, Olga Zelenaia, Shangzhen Zhou, Curt Scribner, Katherine A High, Sara H Renison, Romu Corbau
Journal: Molecular Therapy (2012)

The hepatitis C virus (HCV) chronically infects 2% of the world population and effective treatment is limited by long duration and significant side-effects. Here, we describe a novel drug, intended as a "single-shot " therapy, which expresses three short hairpin RNAs (shRNAs) that simultaneously target multiple conserved regions of the HCV genome as confirmed in vitro by knockdown of an HCV replicon system. Using a recombinant adeno-associated virus (AAV) serotype 8 vector for delivery, comprehensive transduction of hepatocytes was achieved in vivo in a nonhuman primate (NHP) model following a single intravenous injection. However, dose ranging studies performed in 13 NHP resulted in high-expression levels of shRNA from wild-type (wt) Pol III promoters and dose-dependent hepatocellular toxicity, the first demonstration of shRNA-related toxicity in primates, establishing that the hepatotoxicity arises from highly conserved features of the RNA interference (RNAi) pathway. In the second generation drug, each promoter was re-engineered to reduce shRNA transcription to levels that circumvent toxicity but still inhibit replicon activity. In vivo testing of this modified construct in 18 NHPs showed conservation of hepatocyte transduction but complete elimination of hepatotoxicity, even with sustained shRNA expression for 50 days. These data support progression to a clinical study for treatment of HCV infection.
Abstract 3925: RNF138, a novel ubiquitin E3 ligase is overexpressed in colon cancer cell lines and interacts with RAD51D
Authors: Brian D. Yard, Michael K. Bedenbaugh, Douglas L. Pittman
Journal: Cancer Research (2010)

Abstract The RAD51 protein family provides core components of the Homologous Recombination (HR) complex, which is critical for repairing DNA double-strand breaks and maintaining genome stability. The purpose of this study was to identify proteins that regulate HR processes through post-translational modification of the RAD51 paralogs. A yeast two-hybrid screen was performed using the RAD51 paralogs RAD51C, RAD51D, and XRCC2 as bait against a normalized universal mouse cDNA library. Fifty-eight primary candidates were isolated, and five are predicted to function in the ubiquitination pathway. Within this group, Ring Finger Protein 138 (RNF138) is of particular interest since RNF138 is a novel E3-ubiquitin ligase having both an N-terminal RING finger domain and a putative C-terminal ubiquitin interaction motif. Presence of both domains indicates RNF138 induces the transfer of ubiquitin to target substrates and also recognizes ubiquitin moieties on other proteins. Expression of RNF138 is increased by 12-fold in the HCC38 breast cancer cell line and 4-fold in SW-48, RKO, and Wi-DR colon cancer cell lines compared to non-tumorigenic controls. Yeast two-hybrid results indicate that RNF138 interaction is unique to RAD51D, as RNF138 failed to directly interact with RAD51C and XRCC2. Further analysis using N- and C-terminal truncated RAD51D constructs revealed that the RAD51D core domain rather than the N-terminal linker region that governs the interaction between RAD51D and XRCC2 mediates the association with RNF138. Moreover, K113A and K113R mutations of the highly conserved RAD51D Walker A ATP binding motif abolished RAD51D-RNF138 association, suggesting that ATP binding and hydrolysis may regulate the interaction. As further demonstration of this association, Myc-RNF138 co-immunoprecipitated with HA-RAD51D following transient transfections. Future studies will determine whether RNF138 is directly required for HR repair and if the mechanism specifically involves RAD51D ubiquitination. Understanding the regulation of HR proteins by ubiquitination processes will provide important insights into cancer progression and guide the identification of new therapeutic strategies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3925.
Abstract 5239: Licoricidin present in licorice root extract inhibits metastatic capacity of 4T1 mouse mammary carcinoma cells <i>in vitro</i> and <i>in vivo</i> systems
Authors: So Young Park, Sujin Kwon, Soon Sung Lim, Jin Kyu Kim, Jong-Sang Kim, Choonghwan Lee, Jung Han Yoon Park
Journal: Cancer Research (2011)

Abstract Licorice root extracts have previously been shown to exhibit anti-carcinogenic activities. However, these extracts harbor considerable quantities of glycyrrhizin, which is known to exert anticarcinogenic activities and also to induce severe hypokalemia and hypertension. In our previous experiments, licoricidin was identified as an antimetastatic active component of a licorice root extract, which contains undetectable amounts of glycyrrhizin. In this study, we evaluated the effects of the licoricidin on the metastatic characteristics of 4T1 murine mammary carcinoma cells. When 4T1 cells were cultured on a transwell-filter in an in vitro model, licoricidin inhibited cell migration in a dose-dependent manner. Gelatin zymography and Western blot analysis showed that licoricidin significantly suppressed the secretion and activation of the matrix metalloproteinase (MMP)-2 and MMP-9. The secretion of tissue inhibitor of metalloproteinase-1 was reduced in licoricidin-treated cells. Licoricidin reduced the protein levels of vascular cell adhesion molecule but did not change intercellular adhesion molecule. To assess the effects of licoricidin on lung metastasis in vivo, we injected 4T1 cells (5×104 cells) into the inguinal mammary fat pads of syngeneic, immunocompetent BALB/c mice. Starting 1 week after 4T1 cell injection, the mice were given daily intraperitoneal injection of licoricidin (2 or 4 mg/kg body weight/day) for 21 days. Licoricidin treatment did not affect solid tumor growth but significantly reduced the number and volume of pulmonary tumor nodules. The expression of interleukin (IL)-1ra, IL-16, interferon γ-inducible protein (IP)-10, chemokine (C-X-C motif) ligand (CXCL)-9, MMP-3, -8, -9, osteopontin, pentraxin-3, stromal cell-derived factor (SDF)-1, and plasminogen activator inhibitor (PAI)-1 was increased in the lung tissues of mice injected with 4T1 cells, which was suppressed by the repeated injections of licoricidin. By contrast, the expression of angiopoietin-1, insulin-like growth factor binding proteins (IGFBP)-9 and IGFBP-10 was decreased in lung tissues of mice injected with 4T1 cells and was increased by the licoricidin treatment. In the present study, using both in vivo and in vitro systems, we have demonstrated that licoricidin profoundly inhibits the metastatic capacity of 4T1 mammary carcinoma cells, which may be mediated via the regulation of several metalloproteases, adhesion molecules, cytokines, and chemokines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5239. doi:10.1158/1538-7445.AM2011-5239
Informed consent in clinical trials. ... it's the law.
Authors: L Gerlis
Journal: BMJ (1993)

is commendable.Since the over 80s are a hetero- geneous group, such a blanket statement as the above must be intolerable.In terms of the risk of bleeding, the Boston area anticoagulation trial, which included subjects aged over 80, reported two deaths from fatal haemorrhage out of 212 patients treated with warfarin.2At the same time the risk reduction for stroke was 86%.In a study of spontaneous intracranial haemorrhage Schutz et al reported only two cases out of 42 as being due to treatment with warfarin.4Tabibian, in an evaluation of acute gastrointestinal bleeding in patients aged 40-89 given anticoagulant drugs, reported that age, duration of anticoagu- lation, degree of prolongation of prothrombin time, and presence or absence of gastrointestinal symptoms were of no value in predicting the risk ofbleeding.5Thus the decision about anticoagulation should be based on a holistic evaluation of the patient and not on age alone.
Effect of physical training on exercise-induced hyperkalemia in chronic heart failure. Relation with ventilation and catecholamines.
Authors: C W Barlow, M S Qayyum, P P Davey, J Conway, D J Paterson, P A Robbins
Journal: Circulation (1994)

BACKGROUND The exercise-induced rise in arterial potassium concentration ([K+]a) may contribute to exercise hyperpnea and could play a role in exertional fatigue. This study was designed to determine whether the exercise-induced rise in [K+]a is altered in patients with chronic heart failure (CHF) and whether physical training affects K+ homeostasis. METHODS AND RESULTS We evaluated 10 subjects with CHF (ejection fraction, 23 +/- 3.9%) and 10 subjects with normal left ventricular function (NLVF) who had undergone previous coronary artery graft surgery (ejection fraction, 63 +/- 8.6%). Subjects performed an incremental cycle ergometer exercise test before and after a physical training or detraining program. Changes in [K+]a and ventilation (VE) during exercise were closely related in both groups. Subjects with CHF did less absolute work and had reduced maximal oxygen consumption (VO2max) compared with subjects with NLVF (P &lt; .01). Exercise-induced rises in [K+]a, VE, norepinephrine, lactate, and heart rate were greater at matched absolute work rates in subjects with CHF than in subjects with NLVF (P &lt; .01). However, when the rise in [K+]a was plotted against percentage of VO2max to match for relative submaximal effort, there were no differences between the two groups. Physical training resulted in reduced exercise-induced hyperkalemia at matched submaximal work rates in both groups (P &lt; .01) despite no associated change in the concentration of arterial catecholamines. At maximal exercise when trained, peak increases in [K+]a were unaltered, but peak concentrations of catecholamines were raised (P &lt; .05). The decrease in VE at submaximal work rates after training was not significant with this incremental exercise protocol, but both groups had an increased peak VE when trained (P &lt; .01). CONCLUSIONS Exercise-induced rises in [K+]a, catecholamines, and VE are greater at submaximal work rates in subjects with CHF than in subjects with NLVF. Physical training reduces the exercise-induced rise in [K+]a but does not significantly decrease VE during submaximal exercise with this incremental cycle ergometry protocol. The reduction in exercise-induced hyperkalemia after training is not the result of altered concentrations of arterial catecholamines. The pathophysiological significance of the increased exercise-induced hyperkalemia in CHF and the mechanisms of improved K+ homeostasis with training have yet to be established.
Function of C/EBPδ in a regulatory circuit that discriminates between transient and persistent TLR4-induced signals
Authors: Vladimir Litvak, Stephen A Ramsey, Alistair G Rust, Daniel E Zak, Kathleen A Kennedy, Aaron E Lampano, Matti Nykter, Ilya Shmulevich, Alan Aderem
Journal: Nature Immunology (2009)