tbuckley/cabot-search huggingface dataset:
Alopecia universalis in liver transplant patients treated with cyclosporin
Authors: M. Monti, M. Barbareschi, R. Caputo
Journal: British Journal of Dermatology (1995)

Journal Article Alopecia universalis in liver transplant patients treated with cyclosporin Get access M. Monti, M. Monti Institute of Dermatologcal Sciences, University of Milan, Via Pace. 9‐20122.Milan, Italy Search for other works by this author on: Oxford Academic Google Scholar M. Barbareschi, M. Barbareschi Institute of Dermatologcal Sciences, University of Milan, Via Pace. 9‐20122.Milan, Italy Search for other works by this author on: Oxford Academic Google Scholar R. Caputo R. Caputo Institute of Dermatologcal Sciences, University of Milan, Via Pace. 9‐20122.Milan, Italy Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 133, Issue 4, 1 October 1995, Pages 663–664, https://doi.org/10.1111/j.1365-2133.1995.tb02731.x Published: 01 October 1995
Effect of Anticoagulants on Experimental Cerebral Infarction
Authors: JACK P. WHISNANT, CLARK H. MILLIKAN, GEORGE P. SAYRE, KHALIL G. WAKIM
Journal: Circulation (1959)

Cerebral infarction is attended by extravasation of blood in varying degrees. The present study was undertaken to learn whether anticoagulant therapy increases the extravasation and thereby diminishes or negates possibly favorable therapeutic effects. A series of experiments on dogs is described and the clinical implications are discussed.
Ethnic differences in the lymphocyte proliferative response induced by a murine IgG1 antibody, Leu-4, to the T3 molecule
Authors: None AboT, A B Tilden, C M Balch, K Kumagai, G M Troup, M D Cooper
Journal: The Journal of Experimental Medicine (1984)

The mitogenic effects of isotypically diverse antibodies to the T3 molecule were examined in genetically diverse population groups. Whereas the OKT3 antibody (IgG2a) was mitogenic for blood mononuclear cells from all individuals tested, the 38.1 antibody (IgM) was consistently nonmitogenic. In contrast, studies of the mitogenic effects of the Leu-4 antibody (IgG1) revealed striking ethnic differences. More than 80% of Caucasians and Negroes were good Leu-4 responders, whereas most individuals of Asian origin, including Indian, Japanese, and Chinese, were either Leu-4 nonresponders or Leu-4 low responders. However, the majority of American Indians, as well as a significant minority of Chinese, were good responders. Cell separation studies confirmed that monocytes govern the different mitogenic effects of the anti-T3 antibodies. The results reveal interesting ethnic differences in monocyte accessory function probably mediated via the Fc-gamma receptor, in the stimulation of T lymphocytes by an IgG1 antibody against the T3 molecule.
Glycogen Synthase Kinase-3 Inactivation Is Not Required for Ischemic Preconditioning or Postconditioning in the Mouse
Authors: Yasuhiro Nishino, Ian G. Webb, Sean M. Davidson, Aminul I. Ahmed, James E. Clark, Sebastien Jacquet, Ajay M. Shah, Tetsuji Miura, Derek M. Yellon, Metin Avkiran, Michael S. Marber
Journal: Circulation Research (2008)

The inactivation of glycogen synthase kinase-3beta (GSK-3beta) is proposed as the event integrating protective pathways initiated by preconditioning and other interventions. The inactivation of GSK-3 is thought to decrease the probability of opening of the mitochondrial permeability transition pore. The aim of this study was to verify the role of GSK-3 using a targeted mouse line lacking the critical N-terminal serine within GSK-3beta (Ser9) and the highly homologous GSK-3alpha (Ser21), which when phosphorylated results in kinase inactivation. Postconditioning with 10 cycles of 5 seconds of reperfusion/5 seconds of ischemia and preconditioning with 6 cycles of 4 minutes of ischemia/6 minutes of reperfusion, similarly reduced infarction of the isolated perfused mouse heart in response to 30 minutes of global ischemia and 120 minutes of reperfusion. Preconditioning caused noticeable inactivating phosphorylation of GSK-3. However, both preconditioning and postconditioning still protected hearts of homozygous GSK-3 double knockin mice. Moreover, direct pharmacological inhibition of GSK-3 catalytic activity with structurally diverse inhibitors before or after ischemia failed to recapitulate conditioning protection. Nonetheless, cyclosporin A, a direct mitochondrial permeability transition pore inhibitor, reduced infarction in hearts from both wild-type and homozygous GSK-3 double knockin mice. Furthermore, in adult cardiac myocytes from GSK-3 double knockin mice, insulin exposure was still as effective as cyclosporin A in delaying mitochondrial permeability transition pore opening. Our results, which include a novel genetic approach, suggest that the inhibition of GSK-3 is unlikely to be the key determinant of cardioprotective signaling in either preconditioning or postconditioning in the mouse.
The Worldwide Prevalence of ADHD: A Systematic Review and Metaregression Analysis
Authors: Guilherme Polanczyk, Maurício Silva de Lima, Bernardo Lessa Horta, Joseph Biederman, Luis Augusto Rohde
Journal: American Journal of Psychiatry (2007)

The worldwide prevalence estimates of attention deficit hyperactivity disorder (ADHD)/hyperkinetic disorder (HD) are highly heterogeneous. Presently, the reasons for this discrepancy remain poorly understood. The purpose of this study was to determine the possible causes of the varied worldwide estimates of the disorder and to compute its worldwide-pooled prevalence.The authors searched MEDLINE and PsycINFO databases from January 1978 to December 2005 and reviewed textbooks and reference lists of the studies selected. Authors of relevant articles from North America, South America, Europe, Africa, Asia, Oceania, and the Middle East and ADHD/HD experts were contacted. Surveys were included if they reported point prevalence of ADHD/HD for subjects 18 years of age or younger from the general population or schools according to DSM or ICD criteria.The literature search generated 9,105 records, and 303 full-text articles were reviewed. One hundred and two studies comprising 171,756 subjects from all world regions were included. The ADHD/HD worldwide-pooled prevalence was 5.29%. This estimate was associated with significant variability. In the multivariate metaregression model, diagnostic criteria, source of information, requirement of impairment for diagnosis, and geographic origin of the studies were significantly associated with ADHD/HD prevalence rates. Geographic location was associated with significant variability only between estimates from North America and both Africa and the Middle East. No significant differences were found between Europe and North America.Our findings suggest that geographic location plays a limited role in the reasons for the large variability of ADHD/HD prevalence estimates worldwide. Instead, this variability seems to be explained primarily by the methodological characteristics of studies.
The Serpin Proteinase Inhibitor 9 Is an Endogenous Inhibitor of Interleukin 1β–Converting Enzyme (Caspase-1) Activity in Human Vascular Smooth Muscle Cells
Authors: James L. Young, Galina K. Sukhova, Don Foster, Walter Kisiel, Peter Libby, Uwe Schönbeck
Journal: The Journal of Experimental Medicine (2000)

Interleukin-1β–converting enzyme (ICE, caspase-1) regulates key steps in inflammation and immunity, by activating the proinflammatory cytokines interleukin (IL-)1β and IL-18, or mediating apoptotic processes. We recently provided evidence for the regulation of caspase-1 activity via an endogenous inhibitor expressed by human vascular smooth muscle cells (SMCs) (Schönbeck, U., M. Herzberg, A. Petersen, C. Wohlenberg, J. Gerdes, H.-D. Flad, and H. Loppnow. 1997. J. Exp. Med. 185:1287–1294). However, the molecular identity of this endogenous inhibitor remained undefined. We report here that the serine proteinase inhibitor (serpin) PI-9 accounts for the endogenous caspase-1 inhibitory activity in human SMCs and prevents processing of the enzyme's natural substrates, IL-1β and IL-18 precursor. Treatment of SMC lysates with anti–PI-9 antibody abrogated the caspase-1 inhibitory activity and coprecipitated the enzyme, demonstrating protein–protein interaction. Furthermore, PI-9 antisense oligonucleotides coordinately reduced PI-9 expression and promoted IL-1β release. Since SMCs comprise the majority of cells in the vascular wall, and because IL-1 is implicated in atherogenesis, we tested the biological validity of our in vitro findings within human atheroma in situ. The unaffected arterial wall contains abundant and homogeneously distributed PI-9. In human atherosclerotic lesions, however, PI-9 expression correlated inversely with immunoreactive IL-1β, supporting a potential role of the endogenous caspase-1 inhibitor in this chronic inflammatory disease. Thus, our results provide new insights into the regulation of this enzyme involved in immune and inflammatory processes of chronic inflammatory diseases, and point to an endogenous antiinflammatory action of PI-9, dysregulated in a prevalent human disease.
Benefit From Procarbazine, Lomustine, and Vincristine in Oligodendroglial Tumors Is Associated With Mutation of <i>IDH</i>
Authors: J. Gregory Cairncross, Meihua Wang, Robert B. Jenkins, Edward G. Shaw, Caterina Giannini, David G. Brachman, Jan C. Buckner, Karen L. Fink, Luis Souhami, Normand J. Laperriere, Jason T. Huse, Minesh P. Mehta, Walter J. Curran
Journal: Journal of Clinical Oncology (2014)

Patients with 1p/19q codeleted anaplastic oligodendroglial tumors who participated in RTOG (Radiation Therapy Oncology Group) 9402 lived much longer after chemoradiotherapy (CRT) than radiation therapy (RT) alone. However, some patients with noncodeleted tumors also benefited from CRT; survival curves separated after the median had been reached, and significantly more patients lived ≥ 10 years after CRT than RT. Thus, 1p/19q status may not identify all responders to CRT.Using trial data, we inquired whether an IDH mutation or germ-line polymorphism associated with IDH-mutant gliomas identified the patients in RTOG 9402 who benefited from CRT.IDH status was evaluable in 210 of 291 patients; 156 (74%) had mutations. rs55705857 was evaluable in 245 patients; 76 (31%) carried the G risk allele. Both were associated with longer progression-free survival after CRT, and mutant IDH was associated with longer overall survival (9.4 v 5.7 years; hazard ratio [HR], 0.59; 95% CI, 0.40 to 0.86; P = .006). For those with wild-type tumors, CRT did not prolong median survival (1.3 v 1.8 years; HR, 1.14; 95% CI, 0.63 to 2.04; P = .67) or 10-year survival rate (CRT, 6% v RT, 4%). Patients with codeleted mutated tumors (14.7 v 6.8 years; HR, 0.49; 95% CI, 0.28 to 0.85; P = .01) and noncodeleted mutated tumors (5.5 v 3.3 years; HR, 0.56; 95% CI, 0.32 to 0.99; P < .05) lived longer after CRT than RT.IDH mutational status identified patients with oligodendroglial tumors who did (and did not) benefit from alkylating-agent chemotherapy with RT. Although patients with codeleted tumors lived longest, patients with noncodeleted IDH-mutated tumors also lived longer after CRT.
S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial
Authors: Wasaburo Koizumi, Hiroyuki Narahara, Takuo Hara, Akinori Takagane, Toshikazu Akiya, Masakazu Takagi, Kosei Miyashita, Takashi Nishizaki, Osamu Kobayashi, Wataru Takiyama, Yasushi Toh, Takashi Nagaie, Seiichi Takagi, Yoshitaka Yamamura, Kimihiko Yanaoka, Hiroyuki Orita, Masahiro Takeuchi
Journal: The Lancet Oncology (2008)
Reduction of bleomycin induced lung fibrosis by candesartan cilexetil, an angiotensin II type 1 receptor antagonist
Authors: M Otsuka
Journal: Thorax (2003)

<b>Background:</b> Signalling of angiotensin II via angiotensin II type 1 receptor (AT1) promotes cardiac and renal fibrosis, but its role in lung fibrosis is little understood. Using a rat bleomycin (BLM) induced model of pulmonary fibrosis, we examined the expression of AT1 in the lung and the effect of an AT1 antagonist on pulmonary fibrosis. <b>Methods:</b> Adult male Sprague-Dawley rats were given 0.3 mg/kg BLM intratracheally. Two days earlier they had received 10 mg/kg/day of the AT1 antagonist candesartan cilexetil mixed in the drinking water. AT1 expression in the lungs was examined by immunohistochemistry and immunoblot methods. The effect of the AT1 antagonist on pulmonary fibrosis was studied by analysis of bronchoalveolar lavage (BAL) fluid, histopathology, and hydroxyproline assay. <b>Results:</b> Immunohistochemical studies showed overexpression of AT1 in inflammatory immune cells, alveolar type II cells, and fibroblasts. A quantitative assay for AT1 showed that AT1 expression was significantly upregulated in cells from BAL fluid after day 3 and in the lung homogenates after day 21. Candesartan cilexetil significantly inhibited the increase in total protein and albumin, as well as the increase in total cells and neutrophils in BAL fluid. On day 21 candesartan cilexetil also ameliorated morphological changes and an increased amount of hydroxyproline in lung homogenates. In addition, BLM increased the expression of transforming growth factor (TGF)-β<sub>1</sub> in BAL fluid on day 7; this increase was significantly reduced by candesartan cilexetil. <b>Conclusion:</b> AT1 expression is upregulated in fibrotic lungs. Angiotensin II promotes lung fibrosis via AT1 and, presumably, in part via TGF-β<sub>1</sub>.
A Role for Common Genomic Variants in the Assessment of Familial Breast Cancer
Authors: Sarah Sawyer, Gillian Mitchell, Joanne McKinley, Georgia Chenevix-Trench, Jonathan Beesley, Xiao Qing Chen, David Bowtell, Alison H. Trainer, Marion Harris, Geoffrey J. Lindeman, Paul A. James
Journal: Journal of Clinical Oncology (2012)

Genome-wide association studies have identified common genomic variants associated with increased susceptibility to breast cancer. In the general population, the risk associated with these known variants seems insufficient to inform clinical management. Their contribution to the development of familial breast cancer is less clear.We studied 1,143 women with breast cancer who had completed BRCA1 and BRCA2 mutation screening as a result of a high risk for hereditary breast cancer. Genotyping of 22 breast cancer-associated genomic variants was performed. A polygenic risk score (PRS), calculated as the sum of the log odds ratios for each allele, was compared with the same metric in 892 controls from the Australian Ovarian Cancer Study. The clinical features associated with the high and low ends of the polygenic risk distribution were compared.Women affected by familial breast cancer had a highly significant excess of risk alleles compared with controls (P = 1.0 × 10(-16)). Polygenic risk (measured by the PRS) was greater in women who tested negative for a BRCA1 or BRCA2 mutation compared with mutation carriers (P = 2.3 × 10(-6)). Non-BRCA1/2 women in the top quartile of the polygenic risk distribution were more likely to have had early-onset breast cancer (< 30 years of age, odds ratio [OR]= 3.37, P = .03) and had a higher rate of second breast cancer (OR 1.96, P = .02) compared with women with low polygenic risk.Genetic testing for common risk variants in women undergoing assessment for familial breast cancer may identify a distinct group of high-risk women in whom the role of risk-reducing interventions should be explored.
LABORATORY TRANSMISSION OF WESTERN EQUINE ENCEPHALOMYELITIS VIRUS BY MOSQUITOES OF THE GENERA CULEX AND CULISETA
Authors: W. McD. Hammon, W. C. Reeves
Journal: The Journal of Experimental Medicine (1943)

1. Western equine virus has been successfully transmitted in the laboratory by 3 species of mosquitoes from 2 genera not previously reported as laboratory vectors: Culex tarsalis, Culiseta inornata, and Culiseta incidens. 2. Though transmission was not demonstrated, survival of the virus for more than a few days was shown to occur in Culex stigmatosoma and Psorophora confinnis. Possibly transmission occurred by the former. 3. In experiments with Culex tarsalis, infection of the mosquitoes occurred from feeding on an inoculated guinea pig, a duck, and virus-blood suspensions. After an incubation period of 10 to 30 days at a temperature above 25 degrees C. these mosquitoes infected chickens and a guinea pig by their bite and virus was in turn demonstrated in the blood of the chickens and in the brain of the guinea pig. A total of 12 transmissions occurred. The fact that mosquitoes can be infected from fowl and in turn transmit to fowl, together with much other supporting data from field and laboratory, is interpreted as strengthening evidence that fowl serve as reservoirs of virus in nature. 4. Since Culex tarsalis mosquitoes have been repeatedly found infected with Western equine virus and epidemiologic evidence supports their incrimination, the vector rôle of this species is now established, and it may be regarded as fully incriminated. 5. Culiseta inornata has also been found infected in nature and now proven a laboratory vector. This species does not fit the epidemiological picture in the Yakima Valley as well as C. tarsalis, but may play an important rôle elsewhere. 6. Anopheles maculipennis freeborni and Culex pipiens found naturally infected have not transmitted the virus under laboratory conditions.
Paradoxical withdrawal of reflex vasoconstriction as a cause of hemodialysis-induced hypotension.
Authors: R L Converse, T N Jacobsen, C M Jost, R D Toto, P A Grayburn, T M Obregon, F Fouad-Tarazi, R G Victor
Journal: Journal of Clinical Investigation (1992)

Acute hypotension is an important complication of hemodialysis, but the underlying mechanisms remain poorly understood. Because hemorrhage-induced hypovolemia can trigger a sudden decrease in sympathetic activity resulting in bradycardia and vasodilation, we hypothesized that hemodialysis-induced hypovolemia also can trigger the same type of vasodepressor reaction, which would exacerbate the volume-dependent fall in blood pressure. We therefore measured blood pressure, vascular resistance, and sympathetic nerve activity (intraneural microelectrodes) during sessions of maintenance hemodialysis in 7 patients with and 16 patients without a history of hemodialysis-induced hypotension. During hemodialysis, blood pressure at first remained unchanged as calf resistance increased in both hypotension-resistant (from 37 +/- 4 to 49 +/- 5 U, P < 0.05) and hypotension-prone (from 42 +/- 6 to 66 +/- 12 U, P < 0.05) patients; sympathetic activity increased comparably in the subset of patients in whom it could be measured. With continued hemodialysis, calf resistance and sympathetic activity increased further in the hypotension-resistant patients, but in the hypotension-prone patients the precipitous decrease in blood pressure was accompanied by decreases in sympathetic activity, vascular resistance, and heart rate as well as symptoms of vasodepressor syncope. On an interdialysis day, both groups of patients increased vascular resistance normally during unloading of cardiopulmonary baroreceptors with lower body negative pressure and increased heart rate normally during unloading of arterial baroreceptors with infusion of nitroprusside. These findings indicate that in a group of hemodialysis patients without diabetes or other conditions known to impair autonomic reflexes, hemodialysis-induced hypotension is not caused by chronic uremic impairment in arterial or cardiopulmonary baroreflexes but rather by acute, paradoxical withdrawal of sympathetic vasoconstrictor drive producing vasodepressor syncope.
Na+–Ca2+ exchanger overexpression predisposes to reactive oxygen species-induced injury
Authors: S Wagner
Journal: Cardiovascular Research (2003)

In heart failure (HF), the generation of reactive oxygen species (ROS) is enhanced. It was shown that failing cardiac myocytes are more susceptible to ROS-induced damage, possibly due to increased expression of the sarcolemmal Na-Ca exchanger (NCX).We investigated the consequences of increased expression levels of NCX in adult rabbit ventricular cardiomyocytes (via adenovirus-mediated gene transfer, Ad-NCX1-GFP) with respect to tolerance towards ROS. After 48-h incubation, cells were monitored for morphological changes on an inverted microscope. ROS were generated via hydrogen peroxide (H(2)O(2)) (100 micromol/l) and Fe(3+)/nitrilotriacetate (Fe(3+)/NTA, 100/200 micromol/l) for 4 min and cell morphology was followed over 30 min. [Na(+)](i) and [Ca(2+)](i) in native cells were measured using SBFI-AM and Indo1-AM, respectively.In native myocytes, exposure to ROS induced hypercontracture. This was accompanied by a 1.3-fold increase in diastolic Indo1 fluorescence ratio (P<0.05). Overexpression of NCX significantly enhanced development of hypercontracture. After 15 min, the percentage of cells that had undergone hypercontracture (F(hyper)) was 85+/-4% vs. only 44+/-10% in control cells (P<0.05). Inhibition of NCX-mediated Ca(2+) entry with KB-R7943 (5 micromol/l) reduced F(hyper) to 33+/-11% (P<0.05). [Na(+)](i) was increased 2.9-fold 1 min prior to hypercontracture (P<0.05).ROS-induced hypercontracture is due to Ca(2+) entry via NCX which could be triggered by a concomitant substantial increase in [Na(+)](i). Elevated NCX levels predispose to ROS-induced injury, a mechanism likely contributing to myocyte dysfunction and death in heart failure.
Airway Lipoxin A<sub>4</sub>Generation and Lipoxin A<sub>4</sub>Receptor Expression Are Decreased in Severe Asthma
Authors: Anna Planagumà, Shamsah Kazani, Gautham Marigowda, Oliver Haworth, Thomas J. Mariani, Elliot Israel, Eugene R. Bleecker, Douglas Curran-Everett, Serpil C. Erzurum, William J. Calhoun, Mario Castro, Kian Fan Chung, Benjamin Gaston, Nizar N. Jarjour, William W. Busse, Sally E. Wenzel, Bruce D. Levy
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Airway inflammation is common in severe asthma despite antiinflammatory therapy with corticosteroids. Lipoxin A(4) (LXA(4)) is an arachidonic acid-derived mediator that serves as an agonist for resolution of inflammation.Airway levels of LXA(4), as well as the expression of lipoxin biosynthetic genes and receptors, in severe asthma.Samples of bronchoalveolar lavage fluid were obtained from subjects with asthma and levels of LXA(4) and related eicosanoids were measured. Expression of lipoxin biosynthetic genes was determined in whole blood, bronchoalveolar lavage cells, and endobronchial biopsies by quantitative polymerase chain reaction, and leukocyte LXA(4) receptors were monitored by flow cytometry.Individuals with severe asthma had significantly less LXA(4) in bronchoalveolar lavage fluids (11.2 +/- 2.1 pg/ml) than did subjects with nonsevere asthma (150.1 +/- 38.5 pg/ml; P < 0.05). In contrast, levels of cysteinyl leukotrienes were increased in both asthma cohorts compared with healthy individuals. In severe asthma, 15-lipoxygenase-1 mean expression was decreased fivefold in bronchoalveolar lavage cells. In contrast, 15-lipoxgenase-1 was increased threefold in endobronchial biopsies, but expression of both 5-lipoxygenase and 15-lipoxygenase-2 in these samples was decreased. Cyclooxygenase-2 expression was decreased in all anatomic compartments sampled in severe asthma. Moreover, LXA(4) receptor gene and protein expression were significantly decreased in severe asthma peripheral blood granulocytes.Mechanisms underlying pathological airway responses in severe asthma include lipoxin underproduction with decreased expression of lipoxin biosynthetic enzymes and receptors. Together, these results indicate that severe asthma is characterized, in part, by defective lipoxin counterregulatory signaling circuits.