tbuckley/cabot-search huggingface dataset:
Pneumonia Acquired in the Community Through Drug-Resistant <i>Streptococcus pneumoniae</i>
Authors: SANTIAGO EWIG, MAURICIO RUIZ, ANTONI TORRES, FRANCESC MARCO, JOSE ANTONIO MARTINEZ, MIGUEL SANCHEZ, JOSEP MENSA
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The aim of the study was to determine the incidence of and risk factors for drug resistance of Streptococcus pneumoniae, and its impact on the outcome among hospitalized patients of pneumococcal pneumonia acquired in the community. Consecutive patients with culture-proven pneumococcal pneumonia were prospectively studied with regard to the incidence of pneumococcal drug resistance, potential risk factors, and in-hospital outcome variables. A total of 101 patients were studied. Drug resistance to penicillin, cephalosporin, or a macrolide drug was found in pneumococci from 52 of the 101 (52%) patients; 49% of these isolates were resistant to penicillin (16% intermediate resistance, 33% high resistance), 31% to cephalosporin (22% intermediate and 9% high resistance), and 27% to a macrolide drug. In immunocompetent patients, age > 65 yr was significantly associated with resistance to cephalosporin (odds ratio [OR]: 5.0; 95% confidence interval [CI]: 1.3 to 18.8, p = 0. 01), and with the presence of > 2 comorbidities with resistance to penicillin (OR: 4.7; 95% CI: 1.2 to 19.1; p < 0.05). In immunosuppressed patients, bacteremia was inversely associated with resistance to penicillin and cephalosporin (OR: 0.04; 95% CI: 0.003 to 0.45; p < 0.005; and OR: 0.46; 95% CI: 0.23 to 0.93; p < 0.05, respectively). Length of hospital stay, severity of pneumonia, and complications were not significantly affected by drug resistance. Mortality was 15% in patients with any drug resistance, as compared with 6% in those without resistance. However, any drug resistance was not significantly associated with death (relative risk [RR]: 2. 5; 95% CI: 0.7 to 8.9; p = 0.14). Moreover, attributable mortality in the presence of discordant antimicrobial treatment was 12%, as compared with 10% (RR: 1.2; 95% CI: 0.3 to 5.3; p = 0.67) in the absence of such treatment. We conclude that the incidence of drug-resistant pneumococci was high. Risk factors for drug resistance included advanced age, comorbidity, and (inversely) bacteremia. Outcome was not significantly affected by drug resistance.
Comparative Long-Term Study of the Toxicities of Free and Liposome-Associated Doxorubicin in Mice After Intravenous Administration&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: A Gabizon, A Meshorer, Y Barenholz
Journal: JNCI Journal of the National Cancer Institute (1986)

The toxicities of free doxorubicin (F-DOX) and liposome-associated doxorubicin (L-DOX) were investigated in inbred BALB/c and outbred Sabra mice treated iv with 5, 7.5, and 10 mg doxorubicin (DOX)/kg body weight every 2 weeks up to 8 injections and observed for 6 months. Sonicated liposomes containing phosphatidylcholine, phosphatidylglycerol, and cholesterol were used. The lethal effect was reduced in mice treated with L-DOX as compared to mice treated with F-DOX. At a dose of 7.5 mg DOX/kg, 100% of mice receiving the L-DOX survived a cumulative dose of 60 mg/kg administered over 98 days, while 92% of mice receiving the F-DOX died. Two distinct patterns of death were observed: an acute phase type occurring early after injection of high doses of DOX and apparently related to gastrointestinal toxicity and a delayed phase type requiring a long latency after initial drug exposure and characterized by a complex pattern of abnormalities. Delivery of DOX by liposomes effectively protected against both types of lethal effects. Reduced toxicity of L-DOX resulted in reduced body and organ weight losses, reduced severity of pathologic changes, and fewer blood biochemical alterations. The pathological damage to the heart muscle found in mice treated with L-DOX was less severe than with F-DOX, and in some cases it was reversible. Nephrotoxicity was extremely frequent and severe among F-DOX-treated mice, while it was totally insignificant among L-DOX-treated mice. Hyperlipidemia, hypoglycemia, and glycogen-depleted hepatocytes were characteristic findings in mice treated with F-DOX. Altogether, the data obtained in this study indicate that liposomes significantly diminish the toxicity of DOX with the use of an intermittent schedule of chemotherapy. In addition to changes in tissue distribution as a mechanism of reduced toxicity, it is proposed that DOX associated with liposomal lipids interacts less efficiently than the free drug with target intracellular phospholipids.
Long-Term Benefit of Early Pre-Reperfusion Metoprolol Administration in Patients With Acute Myocardial Infarction
Authors: Gonzalo Pizarro, Leticia Fernández-Friera, Valentin Fuster, Rodrigo Fernández-Jiménez, José M. García-Ruiz, Ana García-Álvarez, Alonso Mateos, María V. Barreiro, Noemí Escalera, Maite D. Rodriguez, Antonio de Miguel, Inés García-Lunar, Juan J. Parra-Fuertes, Javier Sánchez-González, Luis Pardillos, Beatriz Nieto, Adriana Jiménez, Raquel Abejón, Teresa Bastante, Vicente Martínez de Vega, José A. Cabrera, Beatriz López-Melgar, Gabriela Guzman, Jaime García-Prieto, Jesús G. Mirelis, José Luis Zamorano, Agustín Albarrán, Javier Goicolea, Javier Escaned, Stuart Pocock, Andrés Iñiguez, Antonio Fernández-Ortiz, Vicente Sánchez-Brunete, Carlos Macaya, Borja Ibanez
Journal: Journal of the American College of Cardiology (2014)
Fibroblast Growth Factor 9 Has Oncogenic Activity and Is a Downstream Target of Wnt Signaling in Ovarian Endometrioid Adenocarcinomas
Authors: Neali D. Hendrix, Rong Wu, Rork Kuick, Donald R. Schwartz, Eric R. Fearon, Kathleen R. Cho
Journal: Cancer Research (2006)

Abstract Wnt signaling plays a key role in development and adult tissues via effects on cell proliferation, motility, and differentiation. The cellular response to Wnt ligands largely depends on their ability to stabilize β-catenin and the ability of β-catenin to bind and activate T-cell factor (TCF) transcription factors. Roughly 40% of ovarian endometrioid adenocarcinomas (OEA) have constitutive activation of Wnt signaling as a result of oncogenic mutations in the β-catenin protein or inactivating mutations in key negative regulators of β-catenin, such as the adenomatous polyposis coli and Axin tumor suppressor proteins. We used oligonucleotide microarrays to identify genes of which expression was activated in OEAs with β-catenin dysregulation compared with OEAs lacking Wnt/β-catenin pathway defects. Using microarray and quantitative PCR-based approaches, we found that fibroblast growth factor (FGF9) expression was increased &amp;gt;6-fold in primary OEAs with Wnt/β-catenin pathway defects compared with OEAs lacking such defects. Evidence that β-catenin and TCFs regulate FGF9 expression in several epithelial cell lines was obtained. We found FGF9 was mitogenic for epithelial cells and fibroblasts and FGF9 could stimulate invasion of epithelial and endothelial cells through Matrigel in transwell assays. Furthermore, FGF9 could promote neoplastic transformation of the E1A-immortalized RK3E epithelial cell line, and short hairpin RNA–mediated inhibition of endogenous FGF9 expression in the OEA cell line TOV112D, which carries a β-catenin mutation, inhibited neoplastic growth properties of the cells. Our findings support the notion that FGF9 is a key factor contributing to the cancer phenotype of OEAs carrying Wnt/β-catenin pathway defects. (Cancer Res 2006; 66(3): 1354-62)
Urokinase Receptor (CD87) Regulates Leukocyte Recruitment via β2 Integrins In Vivo
Authors: Andreas E. May, Sandip M. Kanse, Leif R. Lund, Roland H. Gisler, Beat A. Imhof, Klaus T. Preissner
Journal: The Journal of Experimental Medicine (1998)

The urokinase receptor (CD87; uPAR) is found in close association with β2 integrins on leukocytes. We studied the functional consequence of this association for leukocyte adhesion and migration. In vivo, the β2 integrin–dependent recruitment of leukocytes to the inflamed peritoneum of uPAR-deficient mice was significantly reduced as compared with wild-type animals. In vitro, β2 integrin–mediated adhesion of leukocytes to endothelium was lost upon removal of uPAR from the leukocyte surface by phosphatidyl-inositol–specific phospholipase C. Leukocyte adhesion was reconstituted when soluble intact uPAR, but not a truncated form lacking the uPA-binding domain, was allowed to reassociate with the cell surface. uPAR ligation with a monoclonal antibody induced adhesion of monocytic cells and neutrophils to vascular endothelium by six- to eightfold, whereas ligation with inactivated uPA significantly reduced cell-to-cell adhesion irrespective of the β2 integrin–stimulating pathway. These data indicate that β2 integrin–mediated leukocyte–endothelial cell interactions and recruitment to inflamed areas require the presence of uPAR and define a new phenotype for uPAR-deficient mice. Moreover, uPAR ligation differentially modulates leukocyte adhesion to endothelium and provides novel targets for therapeutic strategies in inflammation-related vascular pathologies.
a categorial mutation
Authors: oscar vilarroya
Journal: Behavioral and Brain Sciences (2005)

the proposal of steels &amp; belpaeme (s&amp;b) is on the right track to solve the nativist/empiricist/culturalist controversy. however, their nativist model of colour categorization does not correspond to a proper genetic model. colour perception is the outcome of a complex process of development. a direct correspondence between genes and colour categories cannot be the right approach to the problem.
Subcortical MRI Volumes in Neuroleptic-Naive and Treated Patients With Schizophrenia
Authors: Raquel E. Gur, Veda Maany, P. David Mozley, Charlie Swanson, Warren Bilker, Ruben C. Gur
Journal: American Journal of Psychiatry (1998)

This study examined whether subcortical volumes of the basal ganglia and thalamus in schizophrenic patients are related to neuroleptic exposure and symptom severity.Basal ganglia substructures and thalamic volumes were measured with magnetic resonance imaging in 96 patients with schizophrenia (50 men and 46 women) and 128 healthy comparison subjects (60 men and 68 women). Twenty-one of the patients were neuroleptic-naive; of the 75 previously treated patients, 48 had received typical neuroleptics only, and 27 had received typical and atypical neuroleptics. The relation of volume measures to treatment status, exposure to neuroleptics, and symptoms was examined.The neuroleptic-naive patients did not differ from the healthy comparison subjects in subcortical volumes except for lower thalamic volume. In the neuroleptic-naive group, volumes did not correlate with severity of negative symptoms, but higher volumes in both the thalamus and the putamen were associated with more severe positive symptoms. The previously treated group showed higher volumes in the putamen and globus pallidus than the healthy comparison subjects and the neuroleptic-naive patients. In the treated group, a higher dose of a typical neuroleptic was associated with higher caudate, putamen, and thalamus volumes, whereas a higher dose of an atypical neuroleptic was associated only with higher thalamic volume. Higher subcortical volumes were mildly associated with greater severity of both negative and positive symptoms.Increased subcortical volumes in treated schizophrenic patients seem to be medication-induced hypertrophy. This hypertrophy could reflect structural adaptation to receptor blockade and may moderate the effects of neuroleptic treatment.
Experimental Diabetes Is Associated With Functional Activation of Protein Kinase Cε and Phosphorylation of Troponin I in the Heart, Which Are Prevented by Angiotensin II Receptor Blockade
Authors: Ashwani Malhotra, David Reich, Daniel Reich, Antonio Nakouzi, Vinay Sanghi, David L. Geenen, Peter M. Buttrick
Journal: Circulation Research (1997)

Abstract A cardiomyopathy that is characterized by an impairment in diastolic relaxation and a loss of calcium sensitivity of the isolated myofibril has been described in chronic diabetic animals and humans. To explore a possible role for protein kinase C (PKC)–mediated phosphorylation of myofibrillar proteins in this process, we characterized the subcellular distribution of the major PKC isoforms seen in the adult heart in cardiocytes isolated from diabetic rats and determined patterns of phosphorylation of the major regulatory proteins, including troponin I (TnI). Rats were made diabetic with a single injection of streptozotocin, and myocardiocytes were isolated and studied 3 to 4 weeks later. In nondiabetic animals, 76% of the PKCε isoform was located in the cytosol and 24% was particulate, whereas in diabetic animals, 55% was cytosolic and 45% was particulate ( P &lt;.05). PKCδ, the other major PKC isoform seen in adult cardiocytes, did not show a change in subcellular localization. In parallel, TnI phosphorylation was increased 5-fold in cardiocytes isolated from the hearts of diabetic animals relative to control animals ( P &lt;.01). The change in PKCε distribution and in TnI phosphorylation in diabetic animals was completely prevented by rendering the animals euglycemic with insulin or by concomitant treatment with a specific angiotensin II type-1 receptor (AT 1 ) antagonist. Since PKC phosphorylation of TnI has been associated with a loss of calcium sensitivity of intact myofibrils, these data suggest that angiotensin II receptor–mediated activation of PKC may play a role in the contractile dysfunction seen in chronic diabetes.
Targeting of Bone-Derived Insulin-Like Growth Factor-II by a Human Neutralizing Antibody Suppresses the Growth of Prostate Cancer Cells in a Human Bone Environment
Authors: Taichi Kimura, Takeshi Kuwata, Satoshi Ashimine, Manabu Yamazaki, Chisako Yamauchi, Kanji Nagai, Akashi Ikehara, Yang Feng, Dimiter S. Dimitrov, Seiichi Saito, Atsushi Ochiai
Journal: Clinical Cancer Research (2009)

Advanced prostate cancer frequently involves the bone, where the insulin-like growth factor (IGF)-II is abundant. However, the importance of IGF-II in bone metastasis from prostate cancer is uncertain. The present study was aimed at examining the therapeutic importance of targeting IGF-II in bone metastases from prostate cancer.We investigated whether inhibiting IGF-II using a human neutralizing antibody (m610) suppresses the growth of prostate cancer cells in a human bone environment. Human MDA PCa 2b prostate cancer cells were inoculated into human adult bone implanted into mammary fat pad of nonobese diabetic/severe combined immunodeficient mice or inoculated into mammary fat pad of the mice without human bone implantation. The mice were treated with m610 or a control antibody (m102.4) once weekly for 4 weeks immediately after inoculation with MDA PCa 2b cells.Histomorphologic examination indicated that m610 treatment significantly decreased the MDA PCa 2b tumor area in the human bone compared with the control. Ki-67 immunostaining revealed that the percentage of proliferating cancer cells in the m610-treated bone tumor sections was significantly lower than that in the control. m610 had no effect on MDA PCa 2b tumor growth in the absence of implanted human bone. m610 prevented the in vitro IGF-II-induced proliferation of MDA PCa 2b cells.Our results indicate that IGF-II plays an important role in the prostate cancer cell growth in human bone, suggesting that targeting it by neutralizing antibodies offers a new therapeutic strategy for bone metastasis from prostate cancer.
Abnormal expression of FLI1 protein is an adverse prognostic factor in acute myeloid leukemia
Authors: Steven M. Kornblau, Yi Hua Qiu, Nianxiang Zhang, Neera Singh, Stefan Faderl, Alessandra Ferrajoli, Heather York, Amina A. Qutub, Kevin R. Coombes, Dennis K. Watson
Journal: Blood (2011)
Safety and Health in the Construction Industry
Authors: K Ringen, J Seegal, A England
Journal: Annual Review of Public Health (1995)

Workers in the building, renovation, and demolition of roads and commercial structures in the U.S. suffer a disproportionate share of occupational fatalities and lost-time injuries. Nearly all of the injuries and deaths are preventable. The fatality rate from work-related ailments, such as cancers and silicosis, is believed to be excessive, but is not generally computed. The safety and health problems are tied largely to the construction industry's organization and how the work is performed. Many hazardous exposures result from inadequacies in access to information, measurement technology, and personal protective equipment. Potential solutions are in labor-management site safety and health planning and management, education and training of workers and supervisors, new technologies, federal regulation, workers' compensation law, medical monitoring, and occupational health delivery. Public health opportunities involve health care delivery systems, improved preventive medicine, disability determination and rehabilitation programs, and research, beginning with the standardization of data to monitor these problems.
Association of Serum C‐Reactive Protein Levels With Lupus Disease Activity in the Absence of Measurable Interferon‐α and a C‐Reactive Protein Gene Variant
Authors: Helena Enocsson, Christopher Sjöwall, Alf Kastbom, Thomas Skogh, Maija‐Leena Eloranta, Lars Rönnblom, Jonas Wetterö
Journal: Arthritis & Rheumatology (2014)

The type I interferon (IFN) system is important in the pathogenesis of systemic lupus erythematosus (SLE). We previously demonstrated an inhibitory effect of IFNα on interleukin-6 (IL-6)-induced C-reactive protein (CRP) in vitro, hypothetically explaining the poor correlation between disease activity and CRP levels in SLE. This study was undertaken to investigate disease activity, IL-6 levels, and CRP levels in relation to a CRP gene polymorphism and IFNα.Sera from 155 SLE patients and 100 controls were analyzed for CRP. Patients were genotyped for a CRP single-nucleotide polymorphism (rs1205) associated with low CRP levels. Serum IFNα and IL-6 levels were quantified by immunoassays. Clinical disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K).CRP levels were increased in SLE patients compared to controls, but were not associated with SLEDAI-2K or IL-6 levels. However, exclusion of patients carrying at least one rs1205 minor allele revealed an association between disease activity and CRP levels (P = 0.005). We found a strong association between disease activity and CRP levels (P < 0.0005) when patients with measurable IFNα levels as well as the minor allele of rs1205 were excluded from the analysis. Similarly, when patients with elevated IFNα levels and/or the rs1205 polymorphism were excluded, IL-6 levels were associated with CRP levels.The present study demonstrates that the serum IFNα level as well as the CRP genotype affect the CRP response in SLE patients. Lack of correlation between serum levels of CRP and disease activity could therefore be explained by activation of the type I IFN system and polymorphisms in the CRP gene.
Interactions between Bortezomib and Romidepsin and Belinostat in Chronic Lymphocytic Leukemia Cells
Authors: Yun Dai, Shuang Chen, Lora B. Kramer, Vanessa L. Funk, Paul Dent, Steven Grant
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The goal of this study was to characterize interactions between the proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitors (HDACI) romidepsin or belinostat in chronic lymphocytic leukemia (CLL) cells. Experimental Design: Primary and cultured (JVM-3 and MEC-2) CLL cells were exposed to agents alone or in combination, after which cell death was determined by 7-aminoactinomycin D staining/flow cytometry. Acetylation of target proteins, activation of caspase cascades, and expression of apoptosis-regulatory proteins were monitored by Western blot analysis. Nuclear factor-κB (NF-κB) activity was determined by luciferase reporter assay. Cells were transiently transfected with wild-type and acetylation site-mutated (inactive) RelA(p65) (e.g., K221R, K310R, or K281/221/310R) and assessed for HDACI sensitivity. Results: Combined exposure to very low concentrations of romidepsin or belinostat (i.e., low nanomolar and submicromolar, respectively) in combination with low nanomolar concentrations of bortezomib synergistically induced cell death in primary and cultured CLL cells. These events were likely associated with prevention of HDACI-mediated RelA acetylation and NF-κB activation by bortezomib, down-regulation of antiapoptotic proteins (i.e., Bcl-xL, Mcl-1, and XIAP), as well as up-regulation of the proapoptotic protein Bim, resulting in activation of caspase cascade. Finally, CLL cells transfected with inactive RelA displayed a significant increase in HDACI lethality. Conclusions: Coadministration of the clinically relevant HDACIs romidepsin or belinostat with bortezomib synergistically induces cell death in CLL cells, likely through mechanisms involving, among other factors, NF-κB inactivation and perturbation in the expression of proapoptotic and antiapoptotic proteins. A strategy combining HDAC with proteasome inhibition warrants further attention in CLL.
On Hemianaesthesia of Special and General Sensation
Authors: W. A. Sturge
Journal: BMJ (1878)

five months, with the ultimate cure of her local affection and restora- tion to health.CASE VI.Strict-re of -Internal Os Uteri: Sterizity: Cure.-Mrs.D., one of eleven children, aged 28, had been married five years.Her husband, aged 32, was one of seven children.She enjoyed good health; menstruated every three weeks and three days, the flow lasting four days, moderate in quantity, bright without coagula; it was accom- panied by slight local discomfort.There was no constitutional dis- turbance.The uterus was normal in position and texture; the ex- ternal os was round and cf average size.The sound passed with ease up to the internal os, uwhere it was arrested.Failing on two occasions to overcome the obstacle, I advised the use of the hot vaginal douche, and belladonna suppositories night and morning.After this treatment, I succeeded in passing a small whalebone sound two inches and a half, for which, on withdrawal, I substituted a very small silver stem, soon to be followed by a larger one, which she wore several days.Then the India-rubber stem was introduced and retained for about five months, with little discomfort but great increase to the menstrual flow.Scarcely six months had passed, when she became pregnant, went to the full period, anid was safe!y delivered of a fine child.She has since had excellent health.CASE VII.Cong,)enital Sterility: Cure.-Mrs.E., aged 28, one of six children, married six years, was well developed.Her husband,