tbuckley/cabot-search huggingface dataset:
Clinical Experience With Intravenous and Oral Formulations of the Novel Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid in Patients With Advanced Hematologic Malignancies
Authors: Owen A. O'Connor, Mark L. Heaney, Lawrence Schwartz, Stacie Richardson, Robert Willim, Barbara MacGregor-Cortelli, Tracey Curly, Craig Moskowitz, Carol Portlock, Steven Horwitz, Andrew D. Zelenetz, Stanley Frankel, Victoria Richon, Paul Marks, William K. Kelly
Journal: Journal of Clinical Oncology (2005)

To document the toxicity and activity of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in patients with pretreated hematologic malignancies.Two formulations of SAHA (intravenous [IV] and oral) have been assessed in two consecutive phase I trials. In both trials, dose escalation was performed in parallel and independently in patients with solid tumors and hematologic malignancies. Eligible patients were required to have adequate hepatic and renal function, an absolute neutrophil count > or = 500/microL and a platelet count more than 25,000/mL. All patients provided informed consent for study inclusion.A total of 39 patients with hematologic malignancy were enrolled (14 on IV SAHA and 25 on oral SAHA), of whom 35 were treated. The spectrum of diseases included patients with diffuse large B-cell lymphoma (n = 12), Hodgkin's disease (HD; n = 12), multiple myeloma (n = 2), T-cell lymphoma (n = 3), mantle cell lymphoma (n = 2), small lymphocytic lymphoma (n = 2), and myeloid leukemia (n = 2). Major adverse events with the oral formulation included fatigue, diarrhea, anorexia, and dehydration, whereas myelosuppression and thrombocytopenia were more prominent with the IV formulation. Typically, the hematologic toxicities resolved shortly after SAHA was stopped. There was no neutropenic fever or neutropenic sepsis. Reduction in measurable tumor was observed in five patients. One patient with transformed small lymphocytic lymphoma met criteria for complete response, whereas another met the criteria for partial response (PR). One patient with refractory HD had a PR, whereas three patients had stable disease for up to 9 months.These results suggest that SAHA has activity in hematologic malignancies including HD and select subtypes of non-Hodgkin's lymphoma.
Smoking sophisticates and slobs
Authors: T. Dalrymple
Journal: BMJ (2010)

When I was a student a friend of mine (who has since achieved great eminence) said that one of the consequences of growing old was hardening of the concepts. It was therefore with relief that I discovered recently that I was still capable, despite my advanced years, of learning a new concept.

The notion in question was that of “gratuitous smoking.” I learnt of its existence in a newspaper article about a group of doctors who had called for a ban on smoking in private cars to protect the health of children. According to the report, the doctors also suggested that films with “gratuitous smoking” should be shown only to …
Bringing order to protein disorder through comparative genomics and genetic interactions
Authors: Jeremy Bellay, Sangjo Han, Magali Michaut, TaeHyung Kim, Michael Costanzo, Brenda J Andrews, Charles Boone, Gary D Bader, Chad L Myers, Philip M Kim
Journal: Genome biology (2011)

Abstract Background Intrinsically disordered regions are widespread, especially in proteomes of higher eukaryotes. Recently, protein disorder has been associated with a wide variety of cellular processes and has been implicated in several human diseases. Despite its apparent functional importance, the sheer range of different roles played by protein disorder often makes its exact contribution difficult to interpret. Results We attempt to better understand the different roles of disorder using a novel analysis that leverages both comparative genomics and genetic interactions. Strikingly, we find that disorder can be partitioned into three biologically distinct phenomena: regions where disorder is conserved but with quickly evolving amino acid sequences (flexible disorder); regions of conserved disorder with also highly conserved amino acid sequences (constrained disorder); and, lastly, non-conserved disorder. Flexible disorder bears many of the characteristics commonly attributed to disorder and is associated with signaling pathways and multi-functionality. Conversely, constrained disorder has markedly different functional attributes and is involved in RNA binding and protein chaperones. Finally, non-conserved disorder lacks clear functional hallmarks based on our analysis. Conclusions Our new perspective on protein disorder clarifies a variety of previous results by putting them into a systematic framework. Moreover, the clear and distinct functional association of flexible and constrained disorder will allow for new approaches and more specific algorithms for disorder detection in a functional context. Finally, in flexible disordered regions, we demonstrate clear evolutionary selection of protein disorder with little selection on primary structure, which has important implications for sequence-based studies of protein structure and evolution.
Acute compartment syndrome following non-contact football injury
Authors: P-N Mohanna, F S Haddad
Journal: British Journal of Sports Medicine (1997)

Acute compartment syndrome in athletes, although rare, is a limb threatening condition which warrants emergency treatment. The case of a footballer with acute compartment syndrome of the left lower leg, without any preceding direct trauma to the calf, is reported. To our knowledge this is the only description of acute atraumatic compartment syndrome secondary to rupture of one of the heads of gastrocnemius.
Expression of Thy-1 on human hematopoietic progenitor cells.
Authors: W Craig, R Kay, R L Cutler, P M Lansdorp
Journal: The Journal of Experimental Medicine (1993)

Expression of Thy-1 on hematopoietic cells from human fetal liver (FL), cord blood (CB), and bone marrow (BM) was studied with a novel anti-Thy-1 antibody, 5E10. Specificity of 5E10 for human Thy-1 was demonstrated by immunoprecipitation of a 25-35-kD molecule, and the sequence of a cDNA that was cloned by immunoselection of COS cells transfected with a cDNA library derived from a 5E10+ cell line. Two- and three-color immunofluorescence staining experiments revealed that the Thy-1 expression is restricted to, an average, 1-4% of FL, CB, and BM cells, and binding to these cell types is essentially restricted to a very small subset of lymphoid cells and approximately 25% of CD34+ cells. Thy-1+ CD34+ cells were further characterized as CD38lo/CD45RO+/CD45RA-/CD71lo/c-kit(lo) and rhodamine 123dull. When CD34+ cells were sorted on the basis of Thy-1 expression, the majority of clonogenic cells were recovered in the CD34+Thy-1- fraction, whereas the majority of cells capable of producing myeloid colonies after 5-8 wk of long-term culture (long-term culture initiating cells) were recovered in the Thy-1+CD34+ fraction. In addition to CD34+ cells, Thy-1 was found to be expressed on a variable, very small number (&amp;lt; 1%) of CD34- mononuclear cells in BM, CB, and peripheral blood that were further characterized as CD3+ CD4+ lymphocytes. The restricted expression of Thy-1 on primitive hematopoietic cells is in agreement with a previous report (Baum et al., 1992. Proc. Natl. Acad. Sci. USA. 89:2804) in which Thy-1 expression was used to enrich for primitive hematopoietic cells from fetal tissue. Compared with those previous studies, we found Thy-1 expression on a larger proportion of CD34+ cells (25% in our study vs. 5% in Baum et al.) and furthermore performed studies on Thy-1 expression on CD34+ cells from CB, FL, and BM in relation to markers that are known to be differentially expressed on hematopoietic cells. Taken together our results indicate that Thy-1-specific antibody 5E10 is an attractive tool for further studies on the biology and purification of human stem cells.
Loss of RhoB Expression in Human Lung Cancer Progression
Authors: Julien Mazieres, Teresita Antonia, Ghislaine Daste, Carlos Muro-Cacho, Delphine Berchery, Vanessa Tillement, Anne Pradines, Said Sebti, Gilles Favre
Journal: Clinical Cancer Research (2004)

Abstract Purpose: RhoB is a low molecular weight GTPase belonging to the Ras protein superfamily. Whereas most Rho proteins have been shown to have a positive role in proliferation and malignant transformation, the specific role of RhoB appears more divergent. We reported previously that RhoB inhibits cell proliferation in various human cancer cells. Here, we studied the specific role played by RhoB in human lung cancer. Experimental Design: We analyzed the expression of RhoB protein by immunostaining in human lung tissues ranging from normal to invasive carcinoma from different histological types in two large independent studies of, respectively, 94 and 45 samples. We then studied the cellular effect of RhoB overexpression in a model of lung cancer (A549, adenocarcinoma) and tumorigenicity in nude mice. Results: We showed in both studies that RhoB protein was expressed in normal lung and decreased dramatically through lung cancer progression (P &amp;lt; 0.01). Interestingly, RhoB expression was lost in 96% of invasive tumors and reduced by 86% in poorly differentiated tumors compared with the nonneoplastic epithelium. Moreover, the loss of expression of RhoB correlated significantly with tumor stage and proliferative index, whereas no correlation was found between RhoB and p53 or Bcl-2 expression. We then showed that ectopic expression of RhoB in lung cancer cell line A549 suppressed cell proliferation, anchorage-independent growth, and xenograft tumor growth in nude mice. Conclusions: RhoB loss of expression occurs very frequently in lung carcinogenesis, reinforcing its putative tumor suppressive activity, and raising the value of its potential use in cancer therapy.
Single-dose azithromycin versus benzathine benzylpenicillin for treatment of yaws in children in Papua New Guinea: an open-label, non-inferiority, randomised trial
Authors: Oriol Mitjà, Russell Hays, Anthony Ipai, Moses Penias, Raymond Paru, David Fagaho, Elisa de Lazzari, Quique Bassat
Journal: The Lancet (2012)
Stimulation of eosinophil IgE low-affinity receptor leads to increased adhesion molecule expression and cell migration
Authors: S Lantero, G Alessandri, D Spallarossa, L Scarso, GA Rossi
Journal: European Respiratory Journal (2000)

Immunoglobulin binding on eosinophil surface receptors results in activation of these cells. Evaluating blood eosinophils from atopic subjects, it was investigated whether ligation of immunoglobulin E low-affinity receptor (FcepsilonRII/ CD23) with specific monoclonal antibodies (Mabs) resulted in enhanced eosinophil migration and adhesion molecule expression. Eosinophils from 20 subjects with allergic asthma (atopic individuals) and nine nonatopic normal individuals (controls) were purified using Percoll gradients. The effect of antihuman CD23 Mabs on: 1) eosinophil migration through human umbilical vein endothelial cells (HUVECs); and 2) eosinophil expression of the adhesion molecules leukocyte function-associated antigen-1 (LFA-1, CD11a/CD18), macrophage antigen-1 (Mac-1, CD11b/CD18) and very late activation antigen-1 (VLA-4, CD49d/CD29) was evaluated by specific Mab staining and flow cytometric analysis. As compared to controls, freshly isolated eosinophils from atopic individuals showed enhanced migration through HUVECs (p&lt;0.05) and increased LFA-1 expression (p&lt;0.01), but similar Mac-1 and VLA-4 expression (p&gt;0.1 for both). In both controls and atopic individuals, eosinophil incubation with antihuman CD23 Mabs induced a dose-dependent increase in cell migration through HUVECs, significant at antihuman CD23 Mab concentrations of 5 microg x mL(-1) (p&gt;0.05 for all). Similarly, incubation of the cells with antihuman CD23 Mabs induced dose-dependent upregulation of LFA-1 and Mac-1 expression, whereas no changes in VLA-4 expression were observed (p&gt;0.1). Finally, the enhanced eosinophil migration induced by antihuman CD23 Mab stimulation was significantly inhibited by antihuman LFA-1 (84+/-14% (mean+/-SEM); p&lt;0.01) and VLA-4 Mabs (47+/-15%; p&lt;0.05) but not by antihuman Mac-1 Mabs (p&gt;0.1). In both atopic and control subjects, immunoglobulin E, low-affinity receptor stimulation induces functional changes in eosinophils characterized by increased eosinophil migration associated with enhanced late function antigen-1 and Mac-1 expression.
Arsenical polyneuropathy due to caustic arsenical paste.
Authors: T J Robinson
Journal: BMJ (1975)

showing cerebral oedema with diffuse haemorrhagic necrosis micro- scopically and widespread mononuclear cell infiltration of perivascular distribution.The encephalopathy in our case 2 was less severe and not the cause of death, which explains the lack of a characteristic histology.Abnormal liver function values are found in 93% ofcases ofinfectious mononucleosis, with a raised serum bilirubin in 40% and visible jaundice in 17%.The changes are attributed to hepatocellular damage, and in 19 out of 22 cases examined histologically the liver was ab- normal4, usually with mononuclear cell infiltration of portal and sinusoidal areas and scattered focal necrosis, the features seen in case 1.Only two cases of fatal hepatic necrosis convincingly associated with infectious mononucleosis have been described.2Liver histology was similar to that in our case 2, with hepatic necrosis predominantly centrilobular in distribution and mononuclear cell infiltration of portal tracts.Thrombocytopenia, haemolytic anaemia,5 and absolute neutropenia are common incidental findings in infectious mononucleosis but there are eight case reports of extreme neutropenia with recovery in the recent English literature.Only one previous death from infectious mononucleosis complicated by hypoplastic anaemia, agranulocytosis, and septicaemia has been reported.5We are most grateful to Dr. J. D. Crosswell for referring the cases, and to Dr. Joan Edwards, of the Virus Reference Laboratory, Colindale, for her help and advice.
Surface vibration analysis (SVA): a new non-invasive monitor of gastrointestinal activity.
Authors: F C Campbell, B E Storey, P T Cullen, A Cuschieri
Journal: Gut (1989)

A computerised system for measurement of vibration at the abdominal surface was constructed which was addressed to the evaluation of gastrointestinal (GI) motor function. Preliminary studies revealed a dominant low frequency signal which was synchronous with the heartbeat and was considered representative of aortic pulsation. This was excluded by selective spectral filtration. The remaining signal was processed and measured by computer, with provision of quantitative energy values as well as of graphic display. The developed method, called surface vibration analysis (SVA) has been evaluated clinically; (a) against oral to caecal transit times (OCCT) of a standard solid meal, in five patients with severe postgastrectomy diarrhoea, seven patients with mild idiopathic diarrhoea and 22 healthy volunteers. (b) against prokinetic effects of a gastrointestinal stimulant (cisapride) in nine patients. In (a) postprandial SVA energy measurements were greater (SVA [*X (SEM)] = 406,933 (98,224] and oral to caecal transit of the solid meal was more rapid (OCTT = *90 (29) min) in the severe diarrhoea patients [postgastrectomy] than either the mild diarrhoea group (*SVA = 235,317 (50,780); *OCTT = *199 (42) min) or normal volunteers (*SVA = 212,062 (27,153); *OCTT = 242 (19) min) [p less than 0.01 for SVA and OCTT]. In the total group, an inverse correlation was observed between quantitative SVA energy values and oral to caecal transit times of solids (Spearman9s rho = -0.486; p less than 0.01). In (b), drug stimulation of the GI tract caused an increase of fasting SVA measurements from *21,217 (5956) [before] to *41,937 (9606) [after] intravenous cisapride (p less than 0.05). This new technique may be useful for evaluation of gastrointestinal motor activity.
Therapy of interferon-induced depression in chronic hepatitis C with citalopram: a randomised, double-blind, placebo-controlled study
Authors: M R Kraus, A Schafer, K Schottker, C Keicher, B Weissbrich, I Hofbauer, M Scheurlen
Journal: Gut (2007)

<h3>Background:</h3> Interferon-induced depression represents a major complication in antiviral treatment of chronic hepatitis C virus (HCV) infection. <h3>Aim:</h3> To evaluate in a placebo-controlled study the efficacy of a selective serotonin reuptake inhibitor (SSRI) in HCV patients on antiviral therapy with interferon-associated depression. <h3>Methods:</h3> 100 HCV outpatients were included in a randomised, double-blind, placebo-controlled study. During interferon therapy (peginterferon alfa-2b plus ribavirin), depression was monitored using the Hospital Anxiety and Depression Scale (HADS). Patients with clinically relevant interferon-induced depression (HADS ⩾9) were randomly assigned to placebo or citalopram (SSRI, 20 mg/day). <h3>Results:</h3> In 28 patients (28%), HADS scores increased to &gt;8 during interferon therapy. They were treated with placebo (n = 14) or SSRI (n = 14). HADS scores declined significantly in SSRI patients within four weeks of therapy (p&lt;0.001) but not in placebo patients. This difference between subgroups was statistically significant (p = 0.032). Unblinding became necessary in five placebo patients as a result of intolerable depression. Rescue medication (20 mg citalopram) led to a significant decrease in HADS scores (p = 0.008). All citalopram patients were able to complete interferon therapy as planned. As an interim analysis showed a significant superiority of SSRI over placebo, the study was terminated prematurely. Three patients, who became depressed afterwards, were treated in an unblinded fashion with citalopram. <h3>Conclusions:</h3> The findings demonstrate clearly that citalopram treatment is highly effective in HCV patients on interferon therapy, when initiated after the onset of clinically relevant depressive symptoms. This suggests that a general SSRI prophylaxis is not necessary in these patients.
Oxidative Stress–Induced Iron Signaling Is Responsible for Peroxide-Dependent Oxidation of Dichlorodihydrofluorescein in Endothelial Cells
Authors: Yoshiko Tampo, Srigiridhar Kotamraju, Christopher R. Chitambar, Shasi V. Kalivendi, Agnes Keszler, Joy Joseph, B. Kalyanaraman
Journal: Circulation Research (2003)

Dichlorodihydrofluorescein (DCFH) is one of the most frequently used probes for detecting intracellular oxidative stress. In this study, we report that H2O2-dependent intracellular oxidation of DCFH to a green fluorescent product, 2',7'-dichlorofluorescein (DCF), required the uptake of extracellular iron transported through a transferrin receptor (TfR) in endothelial cells. H2O2-induced DCF fluorescence was inhibited by the monoclonal IgA-class anti-TfR antibody (42/6) that blocked TfR endocytosis and the iron uptake. H2O2-mediated inactivation of cytosolic aconitase was responsible for activation of iron regulatory protein-1 and increased expression of TfR, resulting in an increased iron uptake into endothelial cells. H2O2-mediated caspase-3 proteolytic activation was inhibited by anti-TfR antibody. Similar results were obtained in the presence of a lipid hydroperoxide. We conclude that hydroperoxide-induced DCFH oxidation and endothelial cell apoptosis required the uptake of extracellular iron by the TfR-dependent iron transport mechanism and that the peroxide-induced iron signaling, in general, has broader implications in oxidative vascular biology.
Trends and Cardiovascular Mortality Effects of State-Level Blood Pressure and Uncontrolled Hypertension in the United States
Authors: Majid Ezzati, Shefali Oza, Goodarz Danaei, Christopher J.L. Murray
Journal: Circulation (2008)

Blood pressure is an important risk factor for cardiovascular disease and mortality and has lifestyle and healthcare determinants that vary across states. Only self-reported hypertension status is measured at the state level in the United States. Our aim was to estimate levels and trends in state-level mean systolic blood pressure (SBP), the prevalence of uncontrolled systolic hypertension, and cardiovascular mortality attributable to all levels of higher-than-optimal SBP.We estimated the relationship between actual SBP/uncontrolled hypertension and self-reported hypertension, use of blood pressure medication, and a set of health system and sociodemographic variables in the nationally representative National Health and Nutrition Examination Survey. We applied this relationship to identical variables from the Behavioral Risk Factor Surveillance System to estimate state-specific mean SBP and uncontrolled hypertension. We used the comparative risk assessment methods to estimate cardiovascular mortality attributable to higher-than-optimal SBP. In 2001-2003, age-standardized uncontrolled hypertension prevalence was highest in the District of Columbia, Mississippi, Louisiana, Alabama, Texas, Georgia, and South Carolina (18% to 21% for men and 24% to 26% for women) and lowest in Vermont, Minnesota, Connecticut, New Hampshire, Iowa, and Colorado (15% to 16% for men and approximately 21% for women). Women had a higher prevalence of uncontrolled hypertension than men in every state by 4 (Arizona) to 7 (Kansas) percentage points. In the 1990s, uncontrolled hypertension in women increased the most in Idaho and Oregon (by 6 percentage points) and the least in the District of Columbia and Mississippi (by 3 percentage points). For men, the worst-performing states were New Mexico and Louisiana (decrease of 0.6 and 1.3 percentage points), and the best-performing states were Vermont and Indiana (decrease of 4 and 3 percentage points). Age-standardized cardiovascular mortality attributable to higher-than-optimal SBP ranged from 200 to 220 per 100,000 (Minnesota and Massachusetts) to 360 to 370 per 100,000 (District of Columbia and Mississippi) for women and from 210 per 100,000 (Colorado and Utah) to 370 per 100,000 (Mississippi) and 410 per 100,000 (District of Columbia) for men.Lifestyle and pharmacological interventions for lowering blood pressure are particularly needed in the South and Appalachia, and with emphasis on control among women. Self-reported data on hypertension diagnosis from the Behavioral Risk Factor Surveillance System can be used to obtain unbiased state-level estimates of blood pressure and uncontrolled hypertension as benchmarks for priority setting and for designing and evaluating intervention programs.
ACUTE HEMODYNAMIC EFFECT OF TREATMENT WITH ACE INHIBITORS IN PATIENTS WITH SEVERE AORTIC STENOSIS (A PLACEB O CONTROLLED RANDOMIZED STUDY)
Authors: Morten Dalsgaard, Kasper Iversen, Jesper Kjaergaard, Peer Grande, Peter Clemmensen, Jens P. Goetze, Christian Hassager
Journal: Journal of the American College of Cardiology (2011)