tbuckley/cabot-search huggingface dataset:
Transgenic expression of tpr-met oncogene leads to development of mammary hyperplasia and tumors.
Authors: T J Liang, A E Reid, R Xavier, R D Cardiff, T C Wang
Journal: Journal of Clinical Investigation (1996)

Receptor tyrosine kinases are important in cell signal transduction and proliferation. Abnormal expression of tyrosine kinases often leads to malignant transformation. C-met is a tyrosine kinase receptor and its ligand is hepatocyte growth factor (HGF). HGF/c-met plays diverse role in regulation of cell growth, shape and movement. Constitutively activated met, such as tpr-met, is a potent oncogene in vitro, but its carcinogenic role in vivo remains unclear. Our study demonstrates that expression of tpr-met leads to development of mammary tumors and other malignancies in transgenic mice, and suggests that deregulated met expression may be involved in mammary carcinogenesis.
Estrogen Receptor α Phosphorylation on Serine 305, p21-Activated Kinase 1 and Tamoxifen Response in Postmenopausal Breast Cancer.
Authors: J. Bostner, T. Fornander, L. Skoog, B. Nordenskjöld, O. Stål
Journal: Cancer Research (2009)

Abstract Background: Tamoxifen is an adjuvant treatment for estrogen receptor (ER) positive breast cancer. Despite high response rates, resistance is a widespread problem. p21-activated kinase 1 (Pak1) is suggested to phosphorylate the serine 305 residue of the ERα and influence the response to tamoxifen. We aimed to investigate the combination of Pak1 and pERαser305 in relation to treatment prediction and prognosis.Material and Methods: We examined Pak1 and pERαser305 protein by immunohistochemistry in a series of 912 tumors from node negative postmenopausal breast cancer patients randomized to tamoxifen or no adjuvant endocrine treatment.Results: Cytoplasmic Pak1 correlated to large tumors and ER negativity while nuclear Pak1 and pERαser305 correlated to small tumors and ER positivity. Nuclear expression of Pak1 and pERαser305 predicted reduced response to tamoxifen in patients with ERα-positive tumors (tamoxifen versus no tamoxifen, HR=1.33; 95% CI, 0.42-4.2, p=0.63), whereas patients lacking this combination of protein expression in the tumor benefitted significantly from tamoxifen (HR=0.42; 95% CI, 0.29-0.61; p&amp;lt;0.0001). Similar non-significant trends were detected in analyses of the two proteins separately. Pak1 in the cytoplasm was an independent prognostic marker, indicating increased recurrence rate (HR=1.80; 95% CI, 1.18-2.76, p=0.006) and breast cancer mortality (HR=2.02; 95% CI, 1.16-3.52, p=0.014) for patients randomized to no adjuvant treatment.Discussion: Our results suggest that patients with tumors expressing nuclear Pak1 and nuclear pERαser305 in combination represent a subgroup in which tamoxifen treatment is insufficient. Our findings support previous studies showing that Pak1 has differential roles in the cytoplasm and the nucleus. In addition, the Pak1-ER pathway may be of interest as drug target in breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2013.
UPFRONT CLOPIDOGREL USE AND THE EFFICACY AND SAFETY OF EARLY EPTIFIBATIDE USE IN PATIENTS WITH ACUTE CORONARY SYNDROME: AN ANALYSIS FROM THE EARLY VERSUS DELAYED PROVISIONAL EPTIFIBATIDE IN ACUTE CORONARY SYNDROMES (EARLY ACS) TRIAL
Authors: Tracy Wang, Jennifer A. White, Robert P. Giugliano, Pierluigi Tricoci, Robert A. Harrington, Gilles Montalescot, Uwe Zeymer, Frans Van de Werf, Paul W. Armstrong, Eugene Braunwald, Robert M. Califf, L. Kristin Newby
Journal: Journal of the American College of Cardiology (2010)
Capnometric Recirculation Gas Tonometry and Weaning from Mechanical Ventilation
Authors: ABEL MALDONADO, TORSTEN T. BAUER, MIQUEL FERRER, CARMEN HERNANDEZ, FRANCISCO ARANCIBIA, ROBERT RODRIGUEZ-ROISIN, ANTONIO TORRES
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The aim of this study was to describe changes in regional intramucosal Pco 2 (PrCO2 measured with capnometric recirculation gas tonometry [CRGT]) in patients with acute respiratory failure, who proceed from mechanical ventilation to weaning. In addition, we compared the predictive power for the weaning outcome of CRGT measurements obtained during mechanical ventilation to the frequency/ tidal volume (f/Vt) ratio. A total of 24 patients (31 weaning trials) were included in the study, but four of the 24 patients (17%) were excluded because of extubation failure. Of the remaining 27 weaning trials in 20 patients, 12 (44%) were unsuccessful. Changes observed in patients with weaning failure (increase in PrCO2 from 60.4 ± 15.0 mm Hg in mechanical ventilation to 67.4 ± 21.0 mm Hg, in weaning) were significantly different (p = 0.046) from those observed in patients with weaning success (fall in PrCO2 from 61.5 ± 15.0 mm Hg in mechanical ventilation to 56.3 ± 16.7 mm Hg in weaning). However, absolute values of PrCO2 were not significantly different between patients with weaning success and failure, neither during mechanical ventilation (success, 61.5 ± 15.0 versus failure, 60.4 ± 15.0 mm Hg, p = 0.848) nor during weaning (success, 56.3 ± 16.7 versus failure, 67.4 ± 21.0 mm Hg, p = 0.135). The best single predictor for weaning outcome was the f/Vt ratio measured early during weaning (area under the curve: 0.844 ± 0.081; adjusted odds ratio for threshold value ⩽ 105: 42.0, 95% CI 3.8 to 469.1, p = 0.002). CRGT could confirm a significant increase in PrCO2 during weaning in patients who finally failed the weaning trial. However, differences between patients with weaning success and failure were small and CRGT did not replace or improve the predictive power of the f/Vt ratio for weaning outcome. Maldonado A, Bauer TT, Ferrer M, Hernandez C, Arancibia F, Rodriguez-Roisin R, Torres A. Capnometric recirculation gas tonometry and weaning from mechanical ventilation.
Direct comparison of [13N]ammonia and [15O]water estimates of perfusion with quantification of regional myocardial blood flow by microspheres.
Authors: A Bol, J A Melin, J L Vanoverschelde, T Baudhuin, D Vogelaers, M De Pauw, C Michel, A Luxen, D Labar, M Cogneau
Journal: Circulation (1993)

BACKGROUND Both [13N]ammonia and [15O]water have been used to quantify myocardial blood flow with positron emission tomography using appropriate tracer kinetic models. A direct comparison of the two tracers with radioactive microspheres has not been performed in the same experimental preparation. METHODS AND RESULTS The two tracers have been tested for myocardial blood flow quantification in closed-chest dogs with circumflex coronary stenosis or permanent occlusion at rest and during adenosine-induced hyperemia. [13N]ammonia- and [15O]water-derived myocardial blood flow values have been compared with radiolabeled microspheres. Validation studies consisted of simultaneous measurements of blood flow with positron emission tomography and microspheres over a wide range of flow values. Blood pool and regional tissue activity curves were fitted with a three-compartment model for [13N]ammonia with and without arterial metabolite correction and with a single-tissue-compartment model for [15O]water. A correction for finite-resolution effect before the fit was also applied. In large regions of interest (5 cm3), a good correlation between the microsphere method and [13N]ammonia (with metabolite correction) was obtained (y = 3 + 0.78x, r = 0.94). The correlation with microspheres was slightly better with [15O]water (y = -3 + 0.89x, r = 0.97). Similar correlations were achieved in smaller regions of interest (1 cm3) as well as in akinetic segments and in central infarct regions. CONCLUSIONS Positron emission tomography with appropriate tracer kinetic models using [13N]ammonia and [15O]water provides an accurate quantitative method for measuring regional myocardial blood flow over a wide range of flow values in normally contracting or akinetic canine myocardium in the absence and in the presence of infarction.
Update on Acute Lung Injury and Critical Care Medicine 2009
Authors: Michael A. Matthay, Steven Idell
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

This article reviews selected contributions published in 2009 regarding the epidemiology, clinical course, pathogenesis, and treatment of acute lung injury (ALI). Articles in critical care medicine that relate to multiorgan failure are also included. Research on epidemiology and genetic contributions to ALI have opened several promising areas for future studies to establish the environmental and genetic factors that influence its development and outcomes. Novel discoveries have been made on the likely role of platelets and lymphocytes in the pathogenesis and resolution of ALI. Animal and clinical studies have provided new insights regarding the mechanisms that initiate and sustain ALI and the value of both biological and clinical factors for predicting outcome in ALI. Based on preclinical studies, cell-based treatment for ALI, acute renal failure, and septic shock represents a new direction that may eventually have clinical value for therapy of critically ill patients with organ failure. The results of a multicenter randomized trial demonstrated that mortality in critically ill patients was not altered by high- compared with low-intensity renal replacement therapy. In another large randomized trial, tight glucose control worsened mortality in critically ill patients compared with conventional control.

Because the topic is broad, our comments are restricted to a subset of a number of highly meritorious publications, although we included citations for several other articles published in 2009. We primarily focused on discoveries regarding epidemiology, definitions, genetics, clinical course, pathogenesis, and new treatments, including publications from both clinical and experimental studies.
Efficacy and Safety of Latanoprost versus Travoprost in Exfoliative Glaucoma Patients
Authors: Anastasios G.P. Konstas, Vassilios P. Kozobolis, Ioannis E. Katsimpris, Kostantinos Boboridis, Stavrenia Koukoula, Jessica N. Jenkins, William C. Stewart
Journal: Ophthalmology (2006)
278.00 Obesity, Not Otherwise Specified
Authors: Elizabeth Toll
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Production of Secretory Diarrhea by Intravenous Infusion of Vasoactive Intestinal Polypeptide
Authors: Mary G. Kane, Thomas M. O'Dorisio, Guenter J. Krejs
Journal: New England Journal of Medicine (1983)

We attempted to reproduce the diarrhea of pancreatic cholera syndrome with prolonged (10-hour) administration of vasoactive intestinal polypeptide (VIP) in five healthy nonfasting subjects. The polypeptide was given as a continuous intravenous infusion at a rate of 400 pmol per kilogram of body weight per hour. By two hours the plasma VIP concentration had risen from a normal basal value of 15.3±0.2 (mean ±S.E.M.) to 129±40 pmol per liter — within the range found in patients with pancreatic cholera syndrome. In each subject profuse watery diarrhea developed within 4.3±0.8 hours (range, 2.0 to 6.3), and the mean stool weight at 10 hours was 2441±600 g (normal 24-hour stool weight, <200 to 250 g). The results of stool analysis were consistent with secretory diarrhea. Between the first and last stool, there were significant increases in fecal sodium and bicarbonate concentrations and in pH. The large fecal bicarbonate loss induced hyperchloremic metabolic acidosis, which is characteristic in patients with pancreatic cholera syndrome. Our study suggests that VIP is not merely a marker of pancreatic cholera, but is the mediator of watery diarrhea in this syndrome. (N Engl J Med 1983; 309:1482–5.)
Identification and Molecular Analysis of Two ApoB Gene Mutations Causing Low Plasma Cholesterol Levels
Authors: Francine K. Welty, Jose Ordovas, Ernst J. Schaefer, Peter W.F. Wilson, Stephen G. Young
Journal: Circulation (1995)

Familial hypobetalipoproteinemia (FHB) is an autosomal codominant disorder characterized by abnormally low plasma levels of apoB and LDL cholesterol. Heterozygotes for FHB almost always have plasma LDL cholesterol levels < 70 mg/dL and are asymptomatic. Because the low cholesterol levels may protect FHB heterozygotes from coronary heart disease, the mechanisms for FHB are of considerable interest.The plasma lipoproteins of 29 subjects with LDL cholesterol levels < 70 mg/dL were examined by SDS-PAGE. One subject who had virtually undetectable levels of LDL cholesterol had a truncated apoB, apoB-44.4, in his lipoproteins; a second subject with an LDL cholesterol level of 44 mg/dL had apoB-55 in his lipoproteins. The apoB-44.4 (2014 amino acids in length) resulted from a frameshift caused by an 11-bp insertion in exon 26 of the apoB gene; the apoB-55 (2494 amino acids) was caused by a nonsense mutation in exon 26 of the apoB gene. The apoB-55 mutation occurred at a CpG dinucleotide pair, a mutational hot spot, and was identical to a mutation described previously in a subject with hypobetalipoproteinemia. Our subject with apoB-55, however, had a different haplotype than the subject described previously, suggesting that the two apoB-55 mutations may have arisen independently. Of note, the apoB-55 proband's father, who had very low cholesterol levels and who probably carried the apoB-55 mutation, had significant coronary and aortic atherosclerosis at autopsy.In a study of adults with low LDL cholesterol levels, we discovered two subjects with truncated apoB proteins and identified the responsible mutations. ApoB gene mutations causing truncated apoB are not particularly rare in subjects with low cholesterol levels. The role of these mutations in preventing atherosclerosis deserves further study.
Efficacy of a toxicity-adjusted topotecan therapy in recurrent small cell lung cancer
Authors: R. M. Huber, M. Reck, H. Gosse, J. von Pawel, J. Mezger, J. G. Saal, R. Kleinschmidt, C. Steppert, H. Steppling
Journal: European Respiratory Journal (2006)

The present prospective multicentre trial investigated whether topotecan, given at a starting dose of 1.25 mg·m -2 with individual dose adjustment, can improve safety in patients with relapsed/refractory small cell lung cancer without loss of efficacy. Patients received topotecan intravenously on days 1–5, every 21 days, for up to six courses. In the absence of relevant haematotoxicities, topotecan was increased to 1.5 mg·m -2 and reduced to 1.0 mg·m -2 in case of severe haematotoxicities. Of 170 recruited patients, 73.2% had stage IV disease and 63.4% had platinum-containing pre-treatment. Patients received a total of 521 courses. In 72.6% of those courses, the dose remained at 1.25 mg·m -2 ; in 9.1% it was reduced and in 18.3% it increased. Overall response rate was 14.1% including one complete response; 28.8% had stable disease. Median duration of response was 13.6 weeks and median survival was 23.4 weeks. Clinical benefit was obvious for sensitive as well as for refractory patients. Haematotoxicity of grade 3 or 4 was clearly lower compared with the standard dose of 1.5 mg·m -2 . In conclusion, topotecan at a dose of 1.25 mg·m -2 appears to be as effective as the dose of 1.5 mg·m -2 , but with reduced toxicity. Since patients with recurrent small cell lung cancer have a poor prognosis, they benefit especially from good tolerability.
Hematopoietic Growth promoting Effects of Natural Killer Cells in Mice in responce to In Vivo Administration of Human Interleukin-2
Authors: William J. Murphy, Dan L. Longo
Journal: JNCI Journal of the National Cancer Institute (1992)

Background : Interleukin-2 (IL-2) is currently being evaluated as an anti-neoplastic agent because of its stimulatory effects on the immune system. However, little is known about the effects of systemic IL-2 administration on hematopoietic parameters. Purpose : Recombinant human IL-2 (rHuIL-2) was administered to mice to evaluate its in vivo hematopoietic effects. The mechanism underlying the effects of rHuIL-2 administration was also determined. Methods : Mice were given 5 × 10 4 IU of rHuIL-2 for 5 days, and their hematopoietic progenitor cell status was determined as measured by growth in soft agar. Antiserum to natural killer (NK) cell-specific markers was used to ascertain if NK cells were responsible for the hematopoietic effects of rHuIL-2. NK cells were purified and cultured in vitro with rHuIL-2 and then adoptively transferred into syngeneic mice to determine the effects on hemato-poiesis. Results : Treatment of mice with rHuIL-2 resulted in a significant increase in bone marrow and splenic hematopoietic progenitor cell content. Mice with severe combined immune deficiency (SCID), which lack T cells and B cells yet have NK cells, also responded to the myelostimulatory effects of rHuIL-2. However, removal of NK cells from the SCID mice with antiserum to NK cell-specific markers abrogated the myelostimulatory properties of rHuIL-2. Adoptive transfer of NK cells that were propagated in vitro with rHuIL-2 into mice also resulted in an increase in splenic hematopoietic progenitor cells. Conclusions : rHuIL-2 exerts significant myelostimulatory effects after in vivo administration, and NK cells are responsible for at least some of these effects. Implications : These results suggest that NK cells and rHuIL-2 may be of use clinically to promote hematopoiesis after bone marrow transplantation or in the face of other myelotoxic therapy in the treatment of cancer. [J Natl Cancer 84: 1195– 1200, 1992]
Vasodepressor carotid sinus syncope.
Authors: T Rentmeester, J Van Zile, M Van Hal, D Levene
Journal: BMJ (1984)

There have been few reports of vasodepressor carotid sinus syncope, as opposed to the cardioinhibitory type, and no definitive treatment has been described. A 58 year old man developed episodes of syncope after surgery and radiotherapy for a laryngeal tumour. The episodes were characterised by hypotension, sharp pain in the right neck, dizziness, and bradycardia. A temporary pacemaker failed to prevent the symptoms, but ephedrine and fludrocortisone produced substantial improvement. Of the four types of treatment used in carotid sinus syncope, irradiation was ruled out because the patient had had irradiation before developing syncope, surgery was inappropriate because of the laryngeal tumour, and pacing failed. Combined drug treatment with a vasoconstrictor and plasma volume expander produced an improvement in symptoms but did not eliminate them.
Circulatory diseases are Europe's biggest killer
Authors: Rory Watson
Journal: BMJ (2006)

Heart attacks, strokes, and other diseases of the circulatory system are the most common cause of death in the European Union, killing two in every five people each year and more than half of those aged over 85.

The findings are from the latest survey into causes of death by Eurostat, the EU’s statistical office. However, the survey, Atlas on Mortality in the European Union which used data for 2001-3, shows major differences in causes of death between countries and across age groups.

Poisoning and external causes of injury, such as road crashes, are the main cause of death among men and boys aged 19 years or under. At 18 deaths per 100 000 people each year, this is 2.4 times the rate in the corresponding female group.

The countries with the highest proportions of deaths caused by transport crashes are Slovakia (19 deaths per 100 000 people), Lithuania (16), and Latvia (15). At the other end of the scale come Sweden (five per 100 000) and the United Kingdom and the Netherlands (six).

Suicide is the second highest external cause of death among those in the ≤19s and the 20-44 age groups. In the first group it accounts for 14% of deaths from external causes among men and 10% among women. In the older group the respective figures are 31% and 32%.

The data show large geographical disparities. The frequency of suicide among 20-44 year olds is lower in southern Europe: five deaths per 100 000 in Greece, 10 in Italy, 11 in Malta, 12 in Spain, and 13 in Portugal. The highest figures for suicide are in northeastern Europe: in Finland (43 deaths per 100 000), Latvia (54), Estonia (55), and Lithuania (90).

In the 45-64 years age group malignant neoplasms are the main cause of death (41% of deaths), followed by diseases of the circulatory system. Numbers of deaths from breast cancer among women were particularly high in the Netherlands (60 per 100 000), the Flemish part of Belgium (64), and Denmark (66) and were low in Spain (38), Greece (38), and Finland (40).

The commonest causes of death among 65-84 year olds are diseases of the circulatory system, including ischaemic heart disease. The survey estimated that almost one million people a year in the EU died from these diseases. The highest figures were in Hungary (2786 deaths per 100 000), Estonia (2881), Slovakia (2970), and Latvia (3061). The lowest were in France (869), Spain (1021), and Italy (1178). This was also the commonest cause of death among people aged over 85.

The survey found that mortality in the 15 older EU member countries (members before 2004) as well as Cyprus, Malta, and Slovenia was close to or below the overall European average mortality but that Hungary and Poland had excess mortality, particularly among those aged ≥35. Lithuania, Estonia, and Latvia had very high excess mortality among people aged up to 64 years, while Slovakia had high excess mortality among those aged ≤14 and those aged 30-64 and the Czech Republic among those aged ≥45.
Metastatic Soft Tissue Calcification in Chronic Renal Failure Detected by Radionuclide Imaging
Authors: A AHSAN EJAN, NIGHAT NISAR, VASANT C. GANDHI, DAVID B. EILERS, PARVEZ H. SHIRAZI, TODD S. ING
Journal: Clinical Nuclear Medicine (1995)

Metastatic calcification has been reported in several disease entities, including chronic renal failure. Various imaging modalities have been shown to be useful in the detection of metastatic soft tissue calcification. Radionuclide imaging may detect metastatic soft tissue calcification more readily than routine diagnostic modalities and be a valuable noninvasive method to establish an early diagnosis in high-risk patients. The authors report a patient with extensive soft tissue metastatic calcification who had a myriad of clinical symptoms. The extensive calcification was detected with a radionuclide imaging.
Advances and Challenges in Aerodigestive Epithelial Cancer: Meeting Summary and Research Opportunities
Authors: Jennifer R. Grandis, David P. Carbone, Anil K. Rustgi
Journal: Cancer Research (2007)

Malignant neoplasms arising in the upper aerodigestive tract (encompassing the oral cavity, pharynx, esophagus, larynx, and lung) are among the most common cancers in the United States and worldwide, accounting for nearly one third of all malignancies. These cancers are often fatal despite combined