tbuckley/cabot-search huggingface dataset:
Protection of Human Endothelial Cells From Oxidative Stress
Authors: Giovanni Cuda, Roberto Paternò, Roberto Ceravolo, Mafalda Candigliota, Nicola Perrotti, Francesco Perticone, Maria Concetta Faniello, Filippo Schepis, Antonio Ruocco, Evelina Mele, S. Cassano, Maurizio Bifulco, Mariarosaria Santillo, Enrico V. Avvedimento
Journal: Circulation (2002)

Reactive oxygen species play a critical role in inducing apoptosis. The small GTPase p21 Ras and the ERK1/2 MAPK have been proposed as key regulators of the signaling cascade triggered by oxidative stress (H2O2). Harvey-Ras (Ha-Ras) and Kirsten-Ras (Ki-Ras) isoforms are so far functionally indistinguishable, because they activate the same downstream effectors, including ERK1/2. Moreover, ERK1/2 signaling has been involved in both protection and induction of apoptosis.Human umbilical vein endothelial cells (HUVECs) were subjected to H2O2, and apoptosis was detected by fluorescence-activated cell sorting analysis, fluorescence microscopy, and caspase-3 activation. Transfection of Ha-Ras and Ki-Ras genes in HUVECs was performed to evaluate the response to H2O2. We have found that, whereas Ha-Ras decreases tolerance to oxidative stress, Ki-Ras has a potent antiapoptotic activity. Both effects are mediated by ERK1/2. Tolerance to H2O2 is encoded by a unique stretch of lysines at the COOH terminus of the Ki-Ras, lacking in Ha-Ras, and it is relatively independent of the farnesylated anchor. Inhibition of p21 Ras signaling by farnesylation inhibitors increased the resistance to apoptosis in Ha-Ras-expressing cells.These findings explain the opposite effects of ERK1/2 stimulation on apoptosis found in different cell types and suggest that local activation of ERK1/2 signaling may account for the opposing response to oxidative stress by Ha-Ras or Ki-Ras-expressing cells. Modulation of cell reactivity to oxidative stress by p21 Ras points to the specific and predictive effects of Ras inhibitors in vivo as potential therapeutic drugs in disorders produced by increase of reactive oxygen species inside the cells.
Role of phospholamban phosphorylation on Thr17 in cardiac physiological and pathological conditions
Authors: A MATTIAZZI, C MUNDINAWEILENMANN, C GUOXIANG, L VITTONE, E KRANIAS
Journal: Cardiovascular Research (2005)

The sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) is under the control of a closely associated SR protein named phospholamban (PLN). Dephosphorylated PLN inhibits the SR Ca2+ pump, whereas phosphorylation of PLN, at either Ser16 by PKA or Thr17 by calmodulin-dependent protein kinase II (CaMKII), reverses this inhibition, thus increasing SERCA2a activity and the rate of Ca2+ uptake by the SR. This would in turn lead to an increase in the velocity of relaxation, SR Ca2+ load, and myocardial contractility. Thus, PLN is a major determinant of cardiac contractility and relaxation. Although in the intact heart, β-adrenoceptor stimulation results in phosphorylation of PLN at both Ser16 and Thr17 residues, the role of Thr17 site has long remained equivocal. In this review, we attempt to highlight the signaling cascade and the physiological relevance of the phosphorylation of this residue in the heart under both physiological and pathological situations.
Effect of digitalis on left ventricular function in exercising dogs.
Authors: L D Horwitz, J M Atkins, M Saito
Journal: Circulation Research (1977)

The effect of ouabain on left ventricular function in nonfailing hearts was assessed in 14 chronically instrumented dogs during graded treadmill exercise. At rest, ouabain increased the maximum first derivative of the left ventricular pressure (dp/dtmax) and stroke volume by 38% and 16%, respectively. No change occurred in end-diastolic left ventricular diameter or peak systolic left ventricular pressure. During exercise, ouabain reduced maximum running speed and limited the increments in heart rate and systolic pressure but did not alter dp/dtmax, stroke volume, or end-diastolic diameter. When atropine and ouabain were given and severe exercise was performed, there were no differences from controls in running speed, heart rate, dp/dtmax, or other parameters. When ouabain and propranolol were given dp/dtmax increased at rest and during exercise, compared with results with propranolol alone. It is concluded that the inotropic effect of ouabain is negligible during strenuous physical activity because of the presence of high levels of sympathetic stimulation. However, during exercise in the presence of beta-adrenergic blockade, increases in myocardial contractility do occur in response to ouabain.
Depressive reactions to lung cancer are common and often followed by a poor outcome
Authors: G Buccheri
Journal: European Respiratory Journal (1998)

In diverse human malignancies, including lung cancer, quality of life (QOL) affects the clinical outcome of patients. Many QOL dimensions, however, are influenced by physical status. The current study was undertaken to delineate the role of depression, a state of mind not necessarily influenced by somatic factors. All patients, seen for a newly diagnosed carcinoma of the lung, received a copy of the Self-rating Depression Scale (SDS) proposed by W.W.K. Zung. One hundred and thirty three patients were able and willing to complete the questionnaire. A depression index was calculated, as originally described. Nineteen other prognostically important variables were recorded and available for evaluation. Among the 95 patients who completed all 20 items included in the questionnaire, 53 had an SDS index &lt; or = 50 (no depression), while 42 were moderately or severely depressed (SDS index &gt;50). The survival of depressed patients was significantly lower (p=0.048). Diverse SDS subscales were associated with survival, in either univariate or multivariate analysis. SDS item 19, "I feel that others would be better off if I were dead", emerged as the most significant one. A multivariate model of survival, constructed using only SDS data, had a global Chi-squared value of 29.78, and a p-value of 0.00023. Based on this evidence, it appears that a relationship does exist between patients' depression and prognosis, at least in lung cancer. Further studies are needed to clarify the prognostic effect of depression in more specific (and homogeneous) subgroups of patients.
Translating Birdsong: Songbirds as a Model for Basic and Applied Medical Research
Authors: Michael S. Brainard, Allison J. Doupe
Journal: Annual Review of Neuroscience (2013)

Songbirds, long of interest to basic neuroscience, have great potential as a model system for translational neuroscience. Songbirds learn their complex vocal behavior in a manner that exemplifies general processes of perceptual and motor skill learning and, more specifically, resembles human speech learning. Song is subserved by circuitry that is specialized for vocal learning and production but that has strong similarities to mammalian brain pathways. The combination of highly quantifiable behavior and discrete neural substrates facilitates understanding links between brain and behavior, both in normal states and in disease. Here we highlight (a) behavioral and mechanistic parallels between birdsong and aspects of speech and social communication, including insights into mirror neurons, the function of auditory feedback, and genes underlying social communication disorders, and (b) contributions of songbirds to understanding cortical-basal ganglia circuit function and dysfunction, including the possibility of harnessing adult neurogenesis for brain repair.
Peripheral engraftment of fetal intestine into athymic mice sponsors T cell development: direct evidence for thymopoietic function of murine small intestine.
Authors: R L Mosley, J R Klein
Journal: The Journal of Experimental Medicine (1992)

Adult athymic, lethally irradiated, F1--&amp;gt;parent bone marrow-reconstituted (AT x BM) mice were engrafted bilaterally with day 16-18 fetal intestine or fetal thymus into the kidney capsule and were studied for evidence of peripheral T cell repopulation of 1-12 wk postengraftment. Throughout that time period, both types of grafts were macroscopically and histologically characteristic of differentiated thymus or intestine tissues, respectively. Beginning at week 2 postengraftment, clusters of lymphocytes were present within intestine grafts, particularly in subepithelial regions and in areas below villus crypts. As determined by immunofluorescence staining and flow cytometric analyses, lymphocytes from spleen and lymph nodes of sham-engrafted mice (AT x BM-SHAM) were essentially void of T cells, whereas in AT x BM thymus-engrafted (AT x BM-THG) mice, which served as a positive control for T cell repopulation, normal levels of T cells were present in spleen and lymph nodes by week 3 postengraftment, and at times thereafter. Most striking, however, was the finding that T cell repopulation of the spleen and lymph nodes occurred in AT x BM fetal intestine-engrafted (AT x BM-FIG) mice beginning 3 wk postengraftment. Based on H-2 expression, peripheral T cells in AT x BM-FIG mice were of donor bone marrow origin, and consisted of CD3+, T cell receptor (TCR)-alpha/beta+ T cells with both CD4+8- and CD4-8+ subsets. Peripheral T cells in AT x BM-FIG mice were functionally mature, as demonstrated by their capacity to proliferate after stimulation of CD3 epsilon. Moreover, alloreactive cytotoxic T lymphocytes were generated in primary in vitro cultures of spleen cells from AT x BM-FIG and AT x BM-THG mice, though not in spleen cell cultures from AT x BM-SHAM mice. Histologic studies of engrafted tissues 3-4 wk postengraftment demonstrated that thymus leukemia (Tl) antigens were expressed on epithelial surfaces of intestine grafts, and that both TCR-alpha/beta+ and TCR-gamma/delta+ lymphocytes were present in intestine grafts. Collectively, these findings indicate that the murine small intestine has the capacity to initiate and regulate T cell development from bone marrow precursors, thus providing a mechanism by which extrathymic development of intestine lymphocytes occur.
The Courage to Fail. A Social View of Organ Transplants and Dialysis.
Authors: Renée C. Fox, Judith P. Swazey
Journal: Annals of Internal Medicine (1979)

As a summary of the history of a subject of ever-increasing importance today, this book can be recommended.Dr. Coley brings his narrative up to date, with a terminal chapter on "some techniques of modem biochemistry" and a peep into the future.His book will, therefore, prove useful to the practising biochemist as well as to those more professionally concerned with the history of the subject.Another, and important, attraction to the student is the relatively modest price.
Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries
Authors: H. Kieler, M. Artama, A. Engeland, O. Ericsson, K. Furu, M. Gissler, R. B. Nielsen, M. Norgaard, O. Stephansson, U. Valdimarsdottir, H. Zoega, B. Haglund
Journal: BMJ (2011)

<b>Objective</b> To assess whether maternal use of selective serotonin reuptake inhibitors (SSRIs) increases the risk of persistent pulmonary hypertension in the newborn, and whether such an effect might differ between specific SSRIs. <b>Design</b> Population based cohort study using data from the national health registers. <b>Setting</b> Denmark, Finland, Iceland, Norway, and Sweden, 1996-2007. <b>Participants</b> More than 1.6 million infants born after gestational week 33. <b>Main outcome measures</b> Risks of persistent pulmonary hypertension of the newborn associated with early and late exposure to SSRIs during pregnancy and adjusted for important maternal and pregnancy characteristics. Comparisons were made between infants exposed and not exposed to SSRIs. <b>Results</b> Around 30 000 women had used SSRIs during pregnancy and 11 014 had been dispensed an SSRI later than gestational week 20. Exposure to SSRIs in late pregnancy was associated with an increased risk of persistent pulmonary hypertension in the newborn: 33 of 11 014 exposed infants (absolute risk 3 per 1000 liveborn infants compared with the background incidence of 1.2 per 1000); adjusted odds ratio 2.1 (95% confidence interval 1.5 to 3.0). The increased risks of persistent pulmonary hypertension in the newborn for each of the specific SSRIs (sertraline, citalopram, paroxetine, and fluoxetine) were of similar magnitude. Filling a prescription with SSRIs before gestational week 8 yielded slightly increased risks: adjusted odds ratio 1.4 (95% confidence interval 1.0 to 2.0). <b>Conclusions</b> The risk of persistent pulmonary hypertension of the newborn is low, but use of SSRIs in late pregnancy increases that risk more than twofold. The increased risk seems to be a class effect.
Matrix Metalloproteinase-9 Promoter Polymorphism Associated with Upper Lung Dominant Emphysema
Authors: Isao Ito, Sonoko Nagai, Tomohiro Handa, Shigeo Muro, Toyohiro Hirai, Mitsuhiro Tsukino, Michiaki Mishima
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Matrix metalloproteinase 9 (MMP-9) has proteolytic activity against connective tissue proteins and appears to play an important role in the development of chronic obstructive pulmonary disease (COPD). The functional polymorphism of MMP-9 (C-1562T) is considered as one of the candidate genes in the susceptibility to COPD.To determine if MMP-9 (C-1562T) is related to the development of COPD in the Japanese population and whether it is associated with development of pulmonary emphysema assessed by high-resolution computed tomographic (HRCT) parameters.MMP-9 (C-1562T) genotypes of 84 patients with COPD and 85 healthy smokers (control subjects) were determined by the restriction fragment length polymorphism method. We investigated the relationship between the genotypes using automatically analyzed HRCT parameters, such as percentage of low attenuation area (LAA%) and average computed tomography (CT) value density (Hounsfield units; mean CTv) in upper, middle, and lower lung fields in all patients with COPD.There was no difference in polymorphism of MMP-9 (C-1562T) between patients with COPD and control subjects. In the HRCT study, patients with COPD with a T allele (C/T or T/T) showed larger LAA% (95% confidence interval of difference, 0.5-18.7; p = 0.04), and smaller mean CTv (confidence interval, -34.3 to -1.0; p = 0.04) in the upper lung compared with patients without T alleles (C/C). However, pulmonary function tests showed no difference between the two patient groups. Patients with a T allele showed a decrease in LAA% and an increase in mean CTv from upper to lower lung fields (p = 0.006 and p = 0.002, respectively).Polymorphism of MMP-9 (C-1562T) was associated with upper lung dominant emphysema in patients with COPD.
Lynch syndrome related endometrial cancer: clinical significance beyond the endometrium
Authors: Yiying Wang, Yue Wang, Jie Li, Janiel Cragun, Kenneth Hatch, Setsuko K Chambers, Wenxin Zheng
Journal: Journal of Hematology & Oncology (2013)

Lynch syndrome (LS), an autosomal dominant inherited cancer susceptibility syndrome, also known as hereditary non-polyposis colon cancer (HNPCC), is caused by a germline mutation in one of several DNA mismatch repair (MMR) genes. LS is the most common presentation of hereditary colorectal cancer (CRC), accounting for about 2-5% of all CRC cases. More recently, it is found that a similar number of endometrial cancers is also due to one of the MMR gene mutations. There has been significant progress in LS-related CRC in terms of molecular pathogenesis, risks, genetic basis, and cancer prevention. In contrast, the advance about LS-related endometrial cancer (EC) is very much limited. In this commentary, we summarize the main clinicopathologic features of LS-related EC and propose universal screening for LS in individuals with endometrial cancer.
High endothelial venule binding as a predictor of the dissemination of passaged murine lymphomas.
Authors: R F Bargatze, N W Wu, I L Weissman, E C Butcher
Journal: The Journal of Experimental Medicine (1987)

It has long been postulated that normal lymphocyte homing mechanisms help determine the metastatic spread of lymphoid neoplasms. The traffic of normal lymphocytes is controlled in part by the regulated expression of surface receptors for high endothelial venules (HEV), specialized venules that mediate the extravasation of circulating lymphocytes from the blood into lymphoid organs and sites of chronic inflammation. Here we have compared the in vivo growth patterns of HEV-binding vs. nonbinding murine lymphomas passaged intramuscularly into syngeneic recipients. We report that lymphomas that bind well to HEV (as assessed in a quantitative in vitro assay) disseminate widely via the blood, involving all lymph node groups symmetrically. Although both HEV-binding and nonbinding lymphomas gain access to the blood, gross involvement of lymph nodes by nonbinding lymphomas is limited to nodes draining local tumor at the site of injection, a prominent feature of these lymphomas; distant lymph nodes are not enlarged. The results suggest that the expression of functional receptors for HEV either controls the hematogenous dissemination of malignant lymphocyte populations to HEV-bearing organs, or is coregulated with factors determining this metastatic behavior. The findings support the concept that normal lymphocyte homing mechanisms are important to the spread of leukemias and lymphomas.
How Can I Get a Visa to China?
Authors: E. Grey Dimond
Journal: JAMA (1975)

THERE evidently lurks in the soul of every American an intense yearning to see China. Beginning in the fall of 1971 down to the time in which I write, a week does not pass without my receiving a letter, phone call, or personal query, in varying styles, the essence of which is "How can I get a visa to China?" The variations on the theme are many. Many are straightforward travel enthusiasts who have been everywhere and are accustomed to the habit that an American tourist is surely welcome everywhere, and now want to add China to their travel list. Other queries fall into the category of "I was there in 1941 and I cannot believe that the flies, beggars, famine, etc, have stopped. I want to go look again." Still others have varied reasons: "I collect porcelains and..." "I have to give a report for my book club about
Congestive gastropathy in portal hypertension: Variations in prevalence
Authors: S. W. Hosking
Journal: Hepatology (1989)

Mosaic pattern of gastric mucosa has been reported to be a sensitive and specific criterion for the diagnosis of portal hypertension and an important marker of nonvariceal upper gastrointestinal bleeding. So that the validity of this endoscopic sign could be assessed, 136 patients with portal hypertension, 25 chronic alcoholics without portal hypertension, and 366 controls were carefully endoscoped. Mosaic pattern was significantly ( p &lt; 0.01) more common in portal hypertension patients (7.4%) than in controls (1.4%). It was not seen in chronic alcoholics. The incidence of mosaic pattern was 10.9% in cirrhotics, 2.9% in noncirrhotic portal fibrosis, and 5.4% in extrahepatic portal obstruction patients; the differences were not significant. Mosaic pattern was significantly ( p &lt; 0.01) more often seen in postsclerotherapy (13.8%) than in presclerotherapy patients (2.6%). Bleeding from nonvariceal causes was uncommon, and was seen in only one patient (0.8%) showing mosaic pattern. Endoscopic gastric biopsies from areas showing mosaic pattern did not reveal any vascular abnormalities. In conclusion, gastric mucosal lesions are not very common in Indian patients with portal hypertension. In our experience, “mosaic pattern” is not a useful diagnostic feature in portal hypertension patients.
Immunoglobulin G Fragment C Receptor Polymorphisms and Clinical Efficacy of Trastuzumab-Based Therapy in Patients With HER-2/<i>neu</i>–Positive Metastatic Breast Cancer
Authors: Antonino Musolino, Nadia Naldi, Beatrice Bortesi, Debora Pezzuolo, Marzia Capelletti, Gabriele Missale, Diletta Laccabue, Alessandro Zerbini, Roberta Camisa, Giancarlo Bisagni, Tauro Maria Neri, Andrea Ardizzoni
Journal: Journal of Clinical Oncology (2008)

The anti-HER-2/neu monoclonal antibody trastuzumab has been shown to engage both activatory (fragment C receptor [Fc gamma R]IIIa; Fc gamma RIIa) and inhibitory (Fc gamma RIIb) antibody receptors and Fc gamma R polymorphisms have been identified that may affect the antibody-dependent cell-mediated cytotoxicity (ADCC) of natural-killer cells/monocytes. In this study, we tested whether Fc gamma R polymorphisms are associated with clinical outcome of patients with breast cancer who received trastuzumab.Fifty-four consecutive patients with HER-2/neu-amplified breast cancer receiving trastuzumab plus taxane for metastatic disease were evaluated for genotype for the Fc gamma RIIIa-158 valine(V)/phenylalanine(F), Fc gamma RIIa-131 histidine(H)/arginine(R), and Fc gamma RIIb-232 isoleucine(I)/threonine(T) polymorphisms. Trastuzumab-mediated ADCC of patients' peripheral blood mononuclear cells (PBMCs) was measured by chromium-51 release using a HER-2/neu-expressing human breast cancer cell line as a target. Controls comprised thirty-four patients treated with taxane alone.Our population was in Hardy-Weinberg equilibrium except for the Fc gamma RIIb polymorphism. The Fc gamma RIIIa-158 V/V genotype was significantly correlated with objective response rate (ORR) and progression-free survival (PFS). Also, there was trend significance in ORR and PFS for the Fc gamma RIIa-131 H/H genotype. The combination of the two favorable genotypes (VV and/or H/H) was independently associated with better ORR and PFS compared with the other combinations. The ADCC analysis showed that V/V and/or H/H PBMCs had a significantly higher trastuzumab-mediated cytotoxicity than PBMCs harboring different genotypes.These data support for the first time the hypothesis that Fc gamma R-mediated ADCC plays an important role in the clinical effect of trastuzumab. Prospective studies are needed to confirm the role of Fc gamma R polymorphisms in predicting clinical outcome of patients with breast cancer treated with trastuzumab-based therapy.
Democratisation of scientific advice
Authors: Roland Bal, Wiebe E Bijker, Ruud Hendriks
Journal: BMJ (2005)

a banner headline on the front page of a popular tabloid newspaper read: "Cancer danger of folic acid" on the basis of a paper by Charles et al on taking folate in pregnancy and risk of maternal breast cancer. 1 2 Although coverage in the broadsheets was more balanced, the overall message would inevitably cause concern to women taking folate to reduce the risk of fetal neural tube defect in a desired pregnancy.Despite the likelihood that the most likely explanation for the reported association is chance, as reported in the commentary to the paper, 2 numerous susceptible women will probably not take folate, and some of these may conceive fetuses with neural tube defects.In addition, what company or government will take responsibility for fortification of wheat and corn flour with folate, now that this question has been raised?The authors themselves point out that the numbers are small and the confidence intervals large.The risk was also associated with a much larger dose of folate than is routinely used to reduce the risk of neural tube defects.Those who write such papers and those who publish them cannot disclaim ethical responsibility for how the data are interpreted and must consider more carefully their ethical responsibilities in such situations.