tbuckley/cabot-search huggingface dataset:
Impact of a stepwise introduction of smoke-free legislation on the rate of preterm births: analysis of routinely collected birth data
Authors: B. Cox, E. Martens, B. Nemery, J. Vangronsveld, T. S. Nawrot
Journal: BMJ (2013)

<b>Objective</b> To investigate the incidence of preterm delivery in the Belgian population after implementation of smoke-free legislation in three phases (in public places and most workplaces January 2006, in restaurants January 2007, and in bars serving food January 2010). <b>Design</b> Logistic regression analyses on routinely collected birth data from January 2002 to December 2011. <b>Setting</b> Flanders, Belgium. <b>Population</b> All live born singleton births delivered at 24–44 weeks of gestation (n=606&nbsp;877, with n=448&nbsp;520 spontaneous deliveries). <b>Main outcome measures</b> Preterm birth (gestational age &lt;37 weeks). <b>Results</b> We found reductions in the risk of preterm birth after the introduction of each phase of the smoking ban. No decreasing trend was evident in the years or months before the bans. We observed a step change in the risk of spontaneous preterm delivery of −3.13% (95% CI −4.37% to −1.87%; P&lt;0.01) on 1 January 2007 (ban on smoking in restaurants), and an annual slope change of −2.65% (−5.11% to −0.13%; P=0.04) after 1 January 2010 (ban on smoking in bars serving food). The analysis for all births gave similar results: a step change of −3.18% (−5.38% to −0.94%; P&lt;0.01) on 1 January 2007, and an annual slope change of −3.50% (−6.35% to −0.57%; P=0.02) after 1 January 2010. These changes could not be explained by personal factors (infant sex, maternal age, parity, socioeconomic status, national origin, level of urbanisation); time related factors (underlying trends, month of the year, day of the week); or population related factors (public holidays, influenza epidemics, and short term changes in apparent temperature and particulate air pollution). <b>Conclusion</b> Our study shows a consistent pattern of reduction in the risk of preterm delivery with successive population interventions to restrict smoking. This finding is not definitive but it supports the notion that smoking bans have public health benefits from early life.
Set representations required for the acquisition of the “natural number” concept
Authors: Justin Halberda, Lisa Feigenson
Journal: Behavioral and Brain Sciences (2008)

Abstract Rips et al. consider whether representations of individual objects or analog magnitudes are building blocks for the concept natural number . We argue for a third core capacity – the ability to bind representations of individuals into sets. However, even with this addition to the list of starting materials, we agree that a significant acquisition story is needed to capture natural number.
Effect of thrombin on the fibrinolytic activity of cultured bovine endothelial cells.
Authors: D J Loskutoff
Journal: Journal of Clinical Investigation (1979)

The vascular endothelium is a rich source of plasminogen activator (PA) and thus of blood vessel-associated fibrinolytic activity. Cultured bovine aortic endothelial cells were employed to determine if components of the coagulation system interact with the endothelium to modify expression of this activity. The addition of thrombin to these cultures led to a rapid decline in intracellular PA activity, with as little as 3 ng/ml, or 0.1 nM thrombin causing a 50% decrease within 30 min. Thrombin inactivated with diisopropylflurophosphate or hirudin did not elicit the response. Although control cultures secreted high levels of PA, no PA activity could be detected in the media surrounding the thrombin-treated cells. This loss of activity did not appear to result from direct inactivation of PA by thrombin. These observations indicate that the fibrinolytic potential of cultured endothelial cells is rapidly suppressed by trace amounts of thrombin. The generation of thrombin at sites of vascular injury may have a similar effect on the endothelium.
Decreased cardiac concentration of cGMP kinase in hypertensive animals. An index for cardiac vascularization?
Authors: T Ecker, C Göbel, R Hullin, R Rettig, G Seitz, F Hofmann
Journal: Circulation Research (1989)

Cyclic GMP (cGMP) kinase is intimately involved in the regulation of vascular smooth muscle tone. Its tissue concentration was determined in normotensive and hypertensive rats by use of monospecific anti-cGMP kinase antibodies. Hearts of spontaneously hypertensive rats and renovascular (Goldblatt II) hypertensive rats contained half the concentration of cGMP kinase than those of the respective normotensive animals. The increase in blood pressure and the resulting left ventricular hypertrophy were correlated inversely with the left ventricular cGMP kinase concentration. This decrease was specific for the left ventricle and was not observed in other tissues. In addition, the cardiac concentration of cGMP kinase was unchanged in hyperthyroid animals that had comparable left ventricular hypertrophy and mild hypertension. This suggested that in severe renovascular hypertension the decrease in cardiac cGMP kinase concentration is caused by a relative lack of cardiac vessel growth during the development of hypertrophy. In agreement with this conclusion, immunohistochemistry of cardiac cross sections showed that cGMP kinase was exclusively located in cardiac vessels. In support of this localization, the maximal arterial blood flow of heart, liver, skeletal muscle, and kidney correlated excellently with the cGMP kinase content of the respective organ. These results suggest that the cGMP kinase concentration of nonsmooth muscle tissues depends on the amount of organ-specific vascular smooth muscle and may be used as an index for the vascularization of these organs.
Combination Treatment for Acute Depression Is Superior Only when Psychotherapy Is Added to Medication
Authors: Marc B.J. Blom, Kosse Jonker, Elise Dusseldorp, Philip Spinhoven, Erik Hoencamp, Judith Haffmans, Richard van Dyck
Journal: Psychotherapy and Psychosomatics (2007)

&lt;i&gt;Background:&lt;/i&gt; Although several forms of effective therapy exist for outpatients suffering from major depressive disorder, many patients do not profit from treatment. Combining psychotherapy and medication may be an effective strategy. However, earlier studies have rarely found a clear advantage for the combination. Where an advantage was found, a possible placebo effect of adding 2 types of treatment could not be ruled out as cause for the superior effect of the combination. &lt;i&gt;Methods:&lt;/i&gt; A total of 353 patients were screened, of whom 193 were randomized over 4 conditions: nefazodone plus clinical management, interpersonal psychotherapy (IPT), the combination of the two or the combination of IPT and pill-placebo. All patients suffered from major depressive disorder and had a score of at least 14 on the 17-item Hamilton Rating Scale (HAMD). The patients were treated for 12–16 weeks. At baseline, at 6 weeks and on completion of treatment, ratings were performed by independent raters. The primary outcome measure was the HAMD, and the Montgomery-Asberg Depression Rating Scale (MADRS) the secondary outcome measure. &lt;i&gt;Results:&lt;/i&gt; Of the 193 patients included, 138 completed the trial. All treatments were effective. Using a random regression model, no differences between treatments were found on the HAMD. On the MADRS, however, the combination of medication with psychotherapy was more effective in reducing depressive symptoms compared to medication alone, but not to psychotherapy alone or IPT with pill-placebo. &lt;i&gt;Conclusions:&lt;/i&gt; The results of this study yield support for the use of combining medication with psychotherapy instead of using medication only in the treatment of depressed outpatients. Combination treatment does not have an advantage over psychotherapy alone in the present study.
Critical role of the disintegrin metalloprotease ADAM17 for intestinal inflammation and regeneration in mice
Authors: Athena Chalaris, Nina Adam, Christian Sina, Philip Rosenstiel, Judith Lehmann-Koch, Peter Schirmacher, Dieter Hartmann, Joanna Cichy, Olga Gavrilova, Stefan Schreiber, Thomas Jostock, Vance Matthews, Robert Häsler, Christoph Becker, Markus F. Neurath, Karina Reiß, Paul Saftig, Jürgen Scheller, Stefan Rose-John
Journal: The Journal of Experimental Medicine (2010)

The protease a disintegrin and metalloprotease (ADAM) 17 cleaves tumor necrosis factor (TNF), L-selectin, and epidermal growth factor receptor (EGF-R) ligands from the plasma membrane. ADAM17 is expressed in most tissues and is up-regulated during inflammation and cancer. ADAM17-deficient mice are not viable. Conditional ADAM17 knockout models demonstrated proinflammatory activities of ADAM17 in septic shock via shedding of TNF. We used a novel gene targeting strategy to generate mice with dramatically reduced ADAM17 levels in all tissues. The resulting mice called ADAM17ex/ex were viable, showed compromised shedding of ADAM17 substrates from the cell surface, and developed eye, heart, and skin defects as a consequence of impaired EGF-R signaling caused by failure of shedding of EGF-R ligands. Unexpectedly, although the intestine of unchallenged homozygous ADAM17ex/ex mice was normal, ADAM17ex/ex mice showed substantially increased susceptibility to inflammation in dextran sulfate sodium colitis. This was a result of impaired shedding of EGF-R ligands resulting in failure to phosphorylate STAT3 via the EGF-R and, consequently, in defective regeneration of epithelial cells and breakdown of the intestinal barrier. Besides regulating the systemic availability of the proinflammatory cytokine TNF, our results demonstrate that ADAM17 is needed for vital regenerative activities during the immune response. Thus, our mouse model will help investigate ADAM17 as a potential drug target.
<i>ROS1</i> Rearrangements Define a Unique Molecular Class of Lung Cancers
Authors: Kristin Bergethon, Alice T. Shaw, Sai-Hong Ignatius Ou, Ryohei Katayama, Christine M. Lovly, Nerina T. McDonald, Pierre P. Massion, Christina Siwak-Tapp, Adriana Gonzalez, Rong Fang, Eugene J. Mark, Julie M. Batten, Haiquan Chen, Keith D. Wilner, Eunice L. Kwak, Jeffrey W. Clark, David P. Carbone, Hongbin Ji, Jeffrey A. Engelman, Mari Mino-Kenudson, William Pao, A. John Iafrate
Journal: Journal of Clinical Oncology (2012)

Purpose Chromosomal rearrangements involving the ROS1 receptor tyrosine kinase gene have recently been described in a subset of non–small-cell lung cancers (NSCLCs). Because little is known about these tumors, we examined the clinical characteristics and treatment outcomes of patients with NSCLC with ROS1 rearrangement. Patients and Methods Using a ROS1 fluorescent in situ hybridization (FISH) assay, we screened 1,073 patients with NSCLC and correlated ROS1 rearrangement status with clinical characteristics, overall survival, and when available, ALK rearrangement status. In vitro studies assessed the responsiveness of cells with ROS1 rearrangement to the tyrosine kinase inhibitor crizotinib. The clinical response of one patient with ROS1-rearranged NSCLC to crizotinib was investigated as part of an expanded phase I cohort. Results Of 1,073 tumors screened, 18 (1.7%) were ROS1 rearranged by FISH, and 31 (2.9%) were ALK rearranged. Compared with the ROS1-negative group, patients with ROS1 rearrangements were significantly younger and more likely to be never-smokers (each P &lt; .001). All of the ROS1-positive tumors were adenocarcinomas, with a tendency toward higher grade. ROS1-positive and -negative groups showed no difference in overall survival. The HCC78 ROS1-rearranged NSCLC cell line and 293 cells transfected with CD74-ROS1 showed evidence of sensitivity to crizotinib. The patient treated with crizotinib showed tumor shrinkage, with a near complete response. Conclusion ROS1 rearrangement defines a molecular subset of NSCLC with distinct clinical characteristics that are similar to those observed in patients with ALK-rearranged NSCLC. Crizotinib shows in vitro activity and early evidence of clinical activity in ROS1-rearranged NSCLC.
Chimerism and tolerance to host and donor in severe combined immunodeficiencies transplanted with fetal liver stem cells.
Authors: R Bacchetta, B A Vandekerckhove, J L Touraine, M Bigler, S Martino, L Gebuhrer, J E de Vries, H Spits, M G Roncarolo
Journal: Journal of Clinical Investigation (1993)

We have studied the peripheral T cell repertoire of two patients with severe combined immunodeficiency who were successfully treated with human histocompatibility leukocyte antigen (HLA)-mismatched fetal liver stem cell transplantation. The patients presented a split chimerism. T cells were of donor origin, whereas the B cells/monocytes were of the host phenotype. Interestingly, the natural killer (NK) cells in one patient were donor derived and in the other patient of host origin. The NK cells were functional but did not have antihost or donor reactivity. Despite the HLA mismatch between donor and host cells, complete tolerance was achieved in vivo, and a specific unresponsiveness of peripheral blood mononuclear cells from both patients toward the host cells was demonstrated in vitro. Nevertheless, we could isolate T cell receptor (TCR)alpha beta, CD4+ or CD8+, T cell clones specifically reacting with HLA class I and II molecules of the host. The CD4+ host-reactive T cell clones from both patients produced interleukins 2 and 5, interferon-gamma, granulocyte/macrophage colony-stimulating factor but are specifically defective in interleukin 4 production. The frequencies of CD8+ host-reactive T cells were high, and were in the same range as those observed for CD8+ alloreactive T cells. In contrast, no donor-reactive CD8+ T cells or host or donor-reactive TCR gamma delta + T cells were detected. These data indicate that, after fetal stem cell transplantation, donor-reactive, but not host-reactive cells, are deleted from the T cell repertoire. Therefore, a peripheral mechanism of suppression or clonal anergy, rather than clonal deletion, is involved in maintaining in vivo tolerance toward the host.
Oxidized Phospholipids Induce Phenotypic Switching of Vascular Smooth Muscle Cells In Vivo and In Vitro
Authors: Nataliya A. Pidkovka, Olga A. Cherepanova, Tadashi Yoshida, Matthew R. Alexander, Rebecca A. Deaton, James A. Thomas, Norbert Leitinger, Gary K. Owens
Journal: Circulation Research (2007)

Atherosclerosis is a vascular disease characterized by lipid deposition and inflammation within the arterial wall. Oxidized phospholipids (oxPLs), such as 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (oxPAPC) and its constituents 1-palmytoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) are concentrated within atherosclerotic lesions and are known to be potent proinflammatory mediators. Phenotypic switching of smooth muscle cells (SMCs) plays a critical role in the development, progression, and end-stage clinical consequences of atherosclerosis, yet little is known regarding the effects of specific oxPLs on SMC phenotype. The present studies were focused on determining whether oxPLs regulate expression of SMC differentiation marker genes and the molecular mechanisms involved. Results showed that POVPC and PGPC induced profound suppression of smooth muscle (SM) alpha-actin and SM myosin heavy chain expression while simultaneously increasing expression of MCP-1, MCP-3, and cytolysin. OxPLs also induced nuclear translocation of Krüppel-like transcription factor 4 (KLF4), a known repressor of SMC marker genes. siRNA targeting of KLF4 nearly blocked POVPC-induced suppression of SMC marker genes, and myocardin. POVPC-induced repression of SMC marker genes was also significantly attenuated in KLF4 knockout SMCs. Taken together, these results suggest a novel role for oxPLs in phenotypic modulation of SMCs and indicate that these effects are dependent on the transcription factor, KLF4. These results may have important novel implications for the mechanisms by which oxPLs contribute to the pathogenesis of atherosclerosis.
Maximal respiratory pressures in adult Chinese, Malays and Indians
Authors: A Johan, CC Chan, HP Chia, OY Chan, YT Wang
Journal: European Respiratory Journal (1997)

Maximal static inspiratory and expiratory mouth pressures (PI,max and PE,max, respectively) enable the noninvasive measurement of global respiratory muscle strength. The aim of this study was primarily to obtain normal values of PI,max and PE,max for adult Chinese, Malays and Indians and, secondarily, to study their effect on lung volumes in these subjects. Four hundred and fifty two healthy subjects (221 Chinese, 111 Malays, 120 Indians) were recruited. Measurements of PI,max from residual volume (RV), PE,max from total lung capacity (TLC) and forced vital capacity (FVC) were obtained in the seated position. There were significant ethnic differences in PI,max and PE,max measurements obtained in males, and FVC measurements in both males and females. Chinese males had higher PI,max values (mean (+/-SD) 88.7+/-32.5 cmH2O) and higher PE,max values (113.4+/-41.5) than Malay males (PI,max 74.0+/-22.7 cmH2O, PE,max 94.7+/-23.4 cmH2O). Chinese males had higher PE,max than Indian males (PI,max = 83.7+/-30.0 cmH2O, PE,max 98.4+/-29.2 cmH2O). There were no significant differences among Chinese females (PI,max 53.6+/-2.3 cmH2O, PE,max 68.3+/-24.0 cmH2O), Malay females (PI,max 50.7+/-18.3 cmH2O, PE,max 63.6+/-21.6 cmH2O) and Indian females (PI,max 50.0+/-15.2 cmH2O, PE,max 60.7+/-20.4 cmH2O). In both sexes, the Chinese had a higher FVC compared with Malays and Indians. After adjusting for age, height and weight, race was still a determinant for PE,max in males, and FVC in both sexes. The FVC only correlated weakly with PI,max and PE,max in both sexes. Ethnic differences in respiratory muscle strength, and lung volumes, occur among Asians. However, respiratory muscle strength does not explain the differences in lung volumes in healthy Asian subjects.
Probable Person-to-Person Transmission of Avian Influenza A (H5N1)
Authors: Kumnuan Ungchusak, Prasert Auewarakul, Scott F. Dowell, Rungrueng Kitphati, Wattana Auwanit, Pilaipan Puthavathana, Mongkol Uiprasertkul, Kobporn Boonnak, Chakrarat Pittayawonganon, Nancy J. Cox, Sherif R. Zaki, Pranee Thawatsupha, Malinee Chittaganpitch, Rotjana Khontong, James M. Simmerman, Supamit Chunsutthiwat
Journal: New England Journal of Medicine (2005)

During 2004, a highly pathogenic avian influenza A (H5N1) virus caused poultry disease in eight Asian countries and infected at least 44 persons, killing 32; most of these persons had had close contact with poultry. No evidence of efficient person-to-person transmission has yet been reported. We investigated possible person-to-person transmission in a family cluster of the disease in Thailand.For each of the three involved patients, we reviewed the circumstances and timing of exposures to poultry and to other ill persons. Field teams isolated and treated the surviving patient, instituted active surveillance for disease and prophylaxis among exposed contacts, and culled the remaining poultry surrounding the affected village. Specimens from family members were tested by viral culture, microneutralization serologic analysis, immunohistochemical assay, reverse-transcriptase-polymerase-chain-reaction (RT-PCR) analysis, and genetic sequencing.The index patient became ill three to four days after her last exposure to dying household chickens. Her mother came from a distant city to care for her in the hospital, had no recognized exposure to poultry, and died from pneumonia after providing 16 to 18 hours of unprotected nursing care. The aunt also provided unprotected nursing care; she had fever five days after the mother first had fever, followed by pneumonia seven days later. Autopsy tissue from the mother and nasopharyngeal and throat swabs from the aunt were positive for influenza A (H5N1) by RT-PCR. No additional chains of transmission were identified, and sequencing of the viral genes identified no change in the receptor-binding site of hemagglutinin or other key features of the virus. The sequences of all eight viral gene segments clustered closely with other H5N1 sequences from recent avian isolates in Thailand.Disease in the mother and aunt probably resulted from person-to-person transmission of this lethal avian influenzavirus during unprotected exposure to the critically ill index patient.
Mice Lacking Endothelial Angiotensin-Converting Enzyme Have a Normal Blood Pressure
Authors: Justin Cole, Du Le Quach, Karthik Sundaram, Pierre Corvol, Mario R. Capecchi, Kenneth E. Bernstein
Journal: Circulation Research (2002)

To test the hypothesis that local vascular production of angiotensin II is necessary for the normal regulation of blood pressure, we engineered a new line of genetically altered mice that lack endothelial angiotensin-converting enzyme (ACE). This was accomplished using a novel strategy of targeted homologous recombination to separate the transcriptional control of somatic ACE from its endogenous promoter and to substitute control to the albumin promoter. These new mice, termed ACE.3, do not produce ACE within the lung, the aorta, or any vascular structure. ACE activity within the kidney is only about 14% that of wild-type mice and is limited to tubular epithelium. In contrast, hepatic ACE expression in ACE.3 mice is about 87-fold that of wild-type. The blood pressure, plasma angiotensin II levels, response to ACE inhibitors, and renal function of ACE.3 −/− mice are indistinguishable from littermate wild-type mice. These data show that, under basal conditions, the normal regulation of blood pressure and renal function is possible in a mouse devoid of endothelial ACE.
Trimetazidine Reduces Renal Dysfunction by Limiting the Cold Ischemia/Reperfusion Injury in Autotransplanted Pig Kidneys
Authors: THIERRY HAUET, JEAN-MICHEL GOUJON, ALAIN VANDEWALLE, HERVE BAUMERT, LOUIS LACOSTE, JEAN-PAUL TILLEMENT, MICHEL EUGENE, MICHEL CARRETIER
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Ischemia/reperfusion injury leads to delayed graft function, which is a major problem in kidney transplantation. This study investigated the effects of adding trimetazidine (TMZ) to the perfusate of cold-stored kidneys on the function of reperfused autotransplanted pig kidney. The left kidney was removed and cold-flushed with Euro-Collins (EC), or University of Wisconsin (UW) solutions with or without 10 -6 M TMZ and stored for 48 h at 4°C. The kidneys were then autotransplanted and the contralateral kidneys were removed. Several parameters were analyzed over the 14 d after transplantation. The survival rate was 57% in pigs transplanted with kidneys cold-flushed with UW and 43% for those flushed with EC solution; it was 100% for pigs having kidneys cold-flushed with TMZ-supplemented UW and EC solutions. The functions of the transplanted kidneys were also better preserved after cold flush with TMZ-supplemented solutions than with TMZ-free solutions. Creatinine clearance was higher and the urinary excretion of trimethylamine- N -oxide and dimethylamine, used as markers of renal medulla injury, were lower in animals transplanted with kidneys cold-flushed with TMZ-supplemented solutions than with TMZ-free solutions. The cytoprotective action of TMZ also reduced interstitial and peritubular inflammation and the numbers of infiltrating mononuclear CD45 + and CD3 + T cells. These results indicate that the tissue damage due to ischemia/reperfusion injury may be prevented, at least in part, by adding TMZ to preservation solutions.