tbuckley/cabot-search huggingface dataset:
Intra-articular Prednisolone
Authors: P. H. Kendall
Journal: BMJ (1958)

MEDICAL MEMORANDAorgans.The liver (weight 2,090 g.) was somewhat enlarged and oedematous.Microscopical examination showed mild fatty degeneration and a scanty infiltrate of lymphocytes in the portal tracts.The trachea and main bronchi contained mucopus, and both lobes of the left lung were consolidated.The microscopical picture was that of pneumonia, though only very few polymorphs were found in the inflammatory exudate.There were numerous ulcers in both tonsils and at the base of the tongue.Histological sections showed massive necrosis in the floor of these ulcers, but again there were only very few neutrophils.The bone marrow of the sternum, the vertebral column, and several long bones appeared normal to the naked eye, but smears and sections revealed a complete absence of all myeloid cells, with the exception of a few scattered promyelocytes and eosinophilic myelocytes.The bulk of the cells were erythroblasts and lymphocytes, with a normal distribution of megakaryocytes.COMMENT Tlhe cause of death was undoubtedly agranulocytosis and pneumonia.Jaundice develops in many cases of agranulo- cytosis from all causes, usually as a terminal event.It is therefore difficult to say in this case whether it was due to liver damage from chlorpromazine or to the agranulo- cytosis.It is generally agreed nowadays (" Any Questions," 1957) that regular blood counts can do little to prevent agranulo- cytosis due to drug therapy.The present case therefore underlines once again the need for caution in the administra- tion of drugs of the phenothiazine group.Our thanks are due to Drs.
Bone Marrow Stem Cells Prevent Left Ventricular Remodeling of Ischemic Heart Through Paracrine Signaling
Authors: Ryota Uemura, Meifeng Xu, Nauman Ahmad, Muhammad Ashraf
Journal: Circulation Research (2006)

In this study, we hypothesized that bone marrow stem cells (BMSCs) protect ischemic myocardium through paracrine effects that can be further augmented with preconditioning. In in vitro experiments, cell survival factors such as Akt and eNOS were significantly increased in BMSCs following anoxia. In the second series of experiments following coronary ligation in mice, left ventricles were randomly injected with the following: DMEM (G-1), BMSCs (G-2), and preconditioned BMSCs (G-3). Four days after myocardial infarction, BMSCs were observed within injured myocardium in G-2 and G-3. Apoptotic cardiomyocytes within periinfarct area were significantly reduced in G-3. Four weeks after myocardial infarction, smaller left ventricular (LV) dimension and increased LV ejection fraction were observed in G-3. Infarct area was significantly reduced in G-3. However, GFP + cardiomyocytes were observed in low numbers within periinfarct area in G-2 and G-3. In conclusion, BMSCs secreted cell survival factors under ischemia, and they prevented apoptosis in cardiomyocytes adjacent to the infarcted area. Preconditioning of BMSCs enhanced their survival and ability to attenuate LV remodeling, which was attributable, in part, to paracrine effects.
1131 Effectiveness of aspartate of adenosine as hepatoprotective and anti-fibrotic agent as compared with the parental adenosine
Authors: R HERNANDEZMUNOZSR
Journal: Hepatology (2003)

Substantial interest has focused on the roles of sphingolipid metabolizing enzymes in a variety of hyperproliferative and inflammatory diseases. A key family of enzymes involved in these pathologies is the ceramidases. Ceramidases cleave the pro-apoptotic lipid ceramide into a long-chain fatty acid and sphingosine, which can then be further metabolized to the mitogenic and inflammatory lipid sphingosine 1-phosphate. Consequently, development of ceramidase inhibitors would provide useful pharmacologic probes for further studies of sphingolipid metabolism, as well as lead compounds for drug development. This effort has been hampered by the lack of in vitro and cellular ceramidase assays that are amenable to high-throughput screening. Recently, a fluorogenic ceramide analog has been described as a substrate for use in ceramidase assays. The synthesis of this compound has now been substantially improved in terms of both the required effort and the overall yield of the process. Key improvements include: reduction in number of required steps, use of a hydroboration reaction; incorporation of a Mitsunobu reaction; improved acylation by the addition of triethylamine; together providing a fourfold increase in the overall yield. In addition, it has been demonstrated that the ceramide analog can be used in high-throughput assays to identify ceramidase inhibitors. Overall, the improved efficiency in the preparation of this ceramidase substrate should accelerate discovery efforts relating to sphingolipid metabolism.
Human leucocyte antigen‐Cw6 as a predictor for clinical response to ustekinumab, an interleukin‐12/23 blocker, in <scp>C</scp> hinese patients with psoriasis: a retrospective analysis
Authors: H.‐Y. Chiu, T.‐S. Wang, C.‐C. Chan, Y.‐P. Cheng, S.‐J. Lin, T.‐F. Tsai
Journal: British Journal of Dermatology (2014)

Ustekinumab, an interleukin-12/23 inhibitor, is effective in the treatment of psoriasis. A recent Italian study showed more favourable response to ustekinumab in patients with positive human leucocyte antigen (HLA)-Cw6. Nonetheless, there are differences in genetic susceptibility to psoriasis between races, and no studies have specifically assessed the candidate genetic markers in predicting therapy outcome in Chinese patients with psoriasis treated with ustekinumab.To determine whether HLA gene polymorphisms can predict the response to ustekinumab in Chinese patients with psoriasis.Sixty-six patients with psoriasis treated with ustekinumab were included in the study, and the effectiveness of ustekinumab therapy was evaluated at weeks 0, 16 and 28 by Psoriasis Area and Severity Index (PASI).More HLA-Cw6-positive patients achieved a PASI 75 response at week 4 compared with HLA-Cw6-negative patients (38% vs. 9%, P = 0·019). Similarly, at week 16, patients carrying the HLA-Cw6 allele showed a higher likelihood of achieving PASI 50, 75 and 90 than Cw6-negative patients, although this was not statistically significant. At week 28, a significantly higher percentage of HLA-Cw6-positive patients maintained PASI 90 response compared with Cw6-negative patients (63% vs. 26%, P = 0·035). Further analysis of other HLA allele polymorphisms did not show significant associations with therapeutic response to ustekinumab.This pharmacogenetic study provides preliminary data indicating that positive HLA-Cw6 is associated with a good response to ustekinumab treatment in Chinese patients with psoriasis.
Placebos in the Treatment of Rheumatoid Arthritis and other Rheumatic Conditions
Authors: E. F. Traut, E. W. Passarelli
Journal: Annals of the Rheumatic Diseases (1957)

Medications and procedures reputedly helpful in treating chronic illnesses such as arthritis are multi- plying to a degree confusing not only to the lay public but also to physicians.Many or most of drugs have come into use empirically.Remissions, often spontaneous and characteristic of rheumatic disease, may coincide with the taking of some advised substance or the performance of some procedure.Autosuggestion and increased security engendered by contact with the healer can result in an improved mental attitude of faith and hope.This can account for improved physiological function which in its turn is conducive to lessening of symptoms or even to remission of the disease.Material Patients seen in the Arthritis Clinic at Cook County Hospital commonly have skeletal disease with chronicity expressed in months or years.They have been exposed to an almost unbelievable number of nostrums, cultists, chemicals, and physical agents, all of which have failed, as evidenced by admission to our clinic. MethodsA complete medical history and physical examina- tion formed part of the first visit.During this study lactose 0 * 3 g.was prescribed to be taken after each meal during the ensuing week of laboratory tests and studies by consulting hospital services.No promise of improvement accompanied the tablets, and such a
Suppression of Mammary Carcinoma Cell Growth by Retinoic Acid: the Cell Cycle Control Gene <i>Btg2</i> Is a Direct Target for Retinoic Acid Receptor Signaling
Authors: Leslie J. Donato, Jean H. Suh, Noa Noy
Journal: Cancer Research (2007)

Abstract The anticarcinogenic activities of retinoic acid (RA) are believed to be mediated by the nuclear RA receptor (RAR) and by the RA-binding protein cellular RA-binding protein-II (CRABP-II). In MCF-7 mammary carcinoma cells, growth inhibition by RA entails an early cell cycle arrest followed by induction of apoptosis. Here, we aimed to obtain insights into the initial cell cycle response. We show that a 3- to 5-h RA pulse is sufficient for inducing a robust growth arrest 2 to 4 days later, demonstrating inhibition of the G1-S transition by RA is triggered by immediate-early RAR targets and does not require the continuous presence of the hormone throughout the arrest program. Expression array analyses revealed that RA induces the expression of several genes involved in cell cycle regulation, including the p53-controlled antiproliferative gene B-cell translocation gene, member 2 (Btg2) and the BTG family member Tob1. We show that induction of Btg2 by RA does not require de novo protein synthesis and is augmented by overexpression of CRABP-II. Additionally, we identify a RA response element in the Btg2 promoter and show that the element binds retinoid X receptor/RAR heterodimers in vitro, is occupied by the heterodimers in cells, and can drive RA-induced activation of a reporter gene. Hence, Btg2 is a novel direct target for RA signaling. In concert with the reports that Btg2 inhibits cell cycle progression by down-regulating cyclin D1, induction of Btg2 by RA was accompanied by a marked decrease in cyclin D1 expression. The observations thus show that the antiproliferative activity of RA in MCF-7 cells is mediated, at least in part, by Btg2. [Cancer Res 2007;67(2):609–15]
Treatment of mantle-cell lymphomas with the VAD +/− chiorambucil regimen with or without subsequent high-dose therapy and peripheral blood stem-cell transplantation
Authors: R. Gressin, E. Legouffe, D. Leroux, M.C. Jacob, P. Swiercz, M. Peoch, V. Capdevilla, J.F. Rossi, A. Thyss, J.J. Sotto
Journal: Annals of Oncology (1997)
Abnormally Reduced Dorsomedial Prefrontal Cortical Activity and Effective Connectivity With Amygdala in Response to Negative Emotional Faces in Postpartum Depression
Authors: Eydie L. Moses-Kolko, Susan B. Perlman, Katherine L. Wisner, Jeffrey James, A. Tova Saul, Mary L. Phillips
Journal: American Journal of Psychiatry (2010)

Postpartum major depression is a significant public health problem that strikes 15% of new mothers and confers adverse consequences for mothers, children, and families. The neural mechanisms involved in postpartum depression remain unknown, but brain processing of affective stimuli appears to be involved in other affective disorders. The authors examined activity in response to negative emotional faces in the dorsomedial pre-frontal cortex and amygdala, key emotion regulatory neural regions of importance to both mothering and depression.Postpartum healthy mothers (N=16) and unmedicated depressed mothers (N=14) underwent functional magnetic resonance imaging blood-oxygen-level-dependent acquisition during a block-designed face versus shape matching task. A two-way analysis of variance was performed examining main effects of condition and group and group-by-condition interaction on activity in bilateral dorsomedial prefrontal cortical and amygdala regions of interest.Depressed mothers relative to healthy mothers had significantly reduced left dorsomedial prefrontal cortical face-related activity. In depressed mothers, there was also a significant negative correlation between left amygdala activity and postpartum depression severity and a significant positive correlation between right amygdala activity and absence of infant-related hostility. There was reliable top-down connectivity from the left dorsomedial prefrontal cortex to the left amygdala in healthy, but not depressed, mothers.Significantly diminished dorsomedial prefrontal cortex activity and dorsomedial prefrontal cortical-amygdala effective connectivity in response to negative emotional faces may represent an important neural mechanism, or effect, of postpartum depression. Reduced amygdala activity in response to negative emotional faces is associated with greater postpartum depression severity and more impaired maternal attachment processes in postpartum depressed mothers.
Liver stiffness is influenced by a standardized meal in patients with chronic hepatitis C virus at different stages of fibrotic evolution
Authors: Umberto Arena, Monica Lupsor Platon, Cristina Stasi, Stefania Moscarella, Alì Assarat, Giorgio Bedogni, Valeria Piazzolla, Radu Badea, Giacomo Laffi, Fabio Marra, Alessandra Mangia, Massimo Pinzani
Journal: Hepatology (2013)

Abstract Transient elastography (TE) is increasingly employed in clinical practice for the noninvasive detection of tissue fibrosis in patients with chronic liver disease (CLD), and particularly chronic hepatitis C virus (HCV)-related hepatitis. The present study was designed to provide a definitive characterization of the “confounding” increase in liver stiffness (LS) following a standardized meal in a consecutive population of 125 patients with chronic HCV infection at different stages of fibrotic evolution. LS values were obtained after overnight fasting and 15, 30, 45, 60, and 120 minutes following the onset of a standardized liquid meal (400 mL, 600 Kcal, 16.7% protein, 53.8% carbohydrates, 29.5% fat). An evident increase in LS values was observed 15 to 45 minutes after the onset of the meal with return to baseline premeal levels within 120 minutes in all patients. The peak postmeal delta increase in LS was progressively more marked with increasing stages of fibrosis ( P &lt; 0.001), becoming maximal in patients with cirrhosis. However, the probability of identifying the Metavir stage of fibrosis, the Child-Pugh class, or the presence/absence of esophageal varices with the postmeal delta increase in LS was inferior to that obtained with baseline LS values. Conclusion : The results of the present study provide definitive evidence of the confounding effect of a meal on the accuracy of LS measurements for the prediction of fibrosis stage in patients with chronic HCV hepatitis and suggest that a fasting period of 120 minutes should be observed before the performance of TE. (HEPATOLOGY 2013;)
Immunochemical characterization of recombinant and native tropomyosins as a new allergen from the house dust mite, Dermatophagoides farinae
Authors: Tsunehiro Aki, Takeshi Kodama, Akihiro Fujikawa, Keisuke Miura, Seiko Shigeta, Takeshi Wada, Toshihiko Jyo, Yoshikatsu Murooka, Satoru Oka, Kazuhisa Ono
Journal: Journal of Allergy and Clinical Immunology (1995)
Burn Treatment for the Unburned
Authors: Basil A. Pruitt
Journal: JAMA (1987)

A burn center, in which the endemic microbial flora varies across time and can cause miniepidemics of life-threatening infections, seems an unlikely site for the care of unburned patients with large open wounds.<sup>1</sup>Heimbach and associates<sup>2</sup>demonstrate that it is in a burn center that patients with toxic epidermal necrolysis (TEN) can receive the wound care needed to prevent further skin injury and the general supportive care needed to minimize the physiological consequences of a large open wound. The treatment employed by the authors emphasizes measures to protect the surface exposed by the epithelial slough from further damage and prevent extension of the depth of the injury. Saline solution is recommended for cleansing the open wound and the entiretỳ of the wound is thereafter covered with a biologic dressing—porcine cutaneous xenografts. Two decades ago, Miller et al<sup>3</sup>demonstrated that prevention of surface desiccation of partial-thickness burns by
Climate Change and Postglacial Human Dispersals in Southeast Asia
Authors: P. Soares, J. A. Trejaut, J.-H. Loo, C. Hill, M. Mormina, C.-L. Lee, Y.-M. Chen, G. Hudjashov, P. Forster, V. Macaulay, D. Bulbeck, S. Oppenheimer, M. Lin, M. B. Richards
Journal: Molecular Biology and Evolution (2008)

Modern humans have been living in Island Southeast Asia (ISEA) for at least 50,000 years.Largely because of the influence of linguistic studies, however, which have a shallow time depth, the attention of archaeologists and geneticists has usually been focused on the last 6,000 years-in particular, on a proposed Neolithic dispersal from China and Taiwan.Here we use complete mitochondrial DNA (mtDNA) genome sequencing to spotlight some earlier processes that clearly had a major role in the demographic history of the region but have hitherto been unrecognized.We show that haplogroup E, an important component of mtDNA diversity in the region, evolved in situ over the last 35,000 years and expanded dramatically throughout ISEA around the beginning of the Holocene, at the time when the ancient continent of Sundaland was being broken up into the present-day archipelago by rising sea levels.It reached Taiwan and Near Oceania more recently, within the last ;8,000 years.This suggests that global warming and sea-level rises at the end of the Ice Age, 15,000-7,000 years ago, were the main forces shaping modern human diversity in the region.
Oncogenic transformation in the absence of Xrcc4 targets peripheral B cells that have undergone editing and switching
Authors: Jing H. Wang, Frederick W. Alt, Monica Gostissa, Abhishek Datta, Michael Murphy, Marat B. Alimzhanov, Kristen M. Coakley, Klaus Rajewsky, John P. Manis, Catherine T. Yan
Journal: The Journal of Experimental Medicine (2008)

Nonhomologous end-joining (NHEJ) repairs DNA double-strand breaks (DSBs) during V(D)J recombination in developing lymphocytes and during immunoglobulin (Ig) heavy chain (IgH) class switch recombination (CSR) in peripheral B lymphocytes. We now show that CD21-cre–mediated deletion of the Xrcc4 NHEJ gene in p53-deficient peripheral B cells leads to recurrent surface Ig-negative B lymphomas (“CXP lymphomas”). Remarkably, CXP lymphomas arise from peripheral B cells that had attempted both receptor editing (secondary V[D]J recombination of Igκ and Igλ light chain genes) and IgH CSR subsequent to Xrcc4 deletion. Correspondingly, CXP tumors frequently harbored a CSR-based reciprocal chromosomal translocation that fused IgH to c-myc, as well as large chromosomal deletions or translocations involving Igκ or Igλ, with the latter fusing Igλ to oncogenes or to IgH. Our findings reveal peripheral B cells that have undergone both editing and CSR and show them to be common progenitors of CXP tumors. Our studies also reveal developmental stage-specific mechanisms of c-myc activation via IgH locus translocations. Thus, Xrcc4/p53-deficient pro–B lymphomas routinely activate c-myc by gene amplification, whereas Xrcc4/p53-deficient peripheral B cell lymphomas routinely ectopically activate a single c-myc copy.
Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial
Authors: Adeel Shahzad, Ian Kemp, Christine Mars, Keith Wilson, Claire Roome, Rob Cooper, Mohammed Andron, Clare Appleby, Mike Fisher, Aleem Khand, Babu Kunadian, Joseph D Mills, John L Morris, William L Morrison, Shahzad Munir, Nick D Palmer, Raphael A Perry, David R Ramsdale, Periaswamy Velavan, Rod H Stables
Journal: The Lancet (2014)
Regulation of TH2 responses by the pulmonary Clara cell secretory 10-kd protein☆
Authors: Chih-Hsing Hung, Li-Chen Chen, Zhongjian Zhang, Bhabadeb Chowdhury, Wan-Ling Lee, Beverly Plunkett, Chien-Ho Chen, Allen C. Myers, Shau-Ku Huang
Journal: Journal of Allergy and Clinical Immunology (2004)
Pairagon+N-SCAN_EST: a model-based gene annotation pipeline.
Authors: Manimozhiyan Arumugam, Chaochun Wei, Randall H Brown, Michael R Brent
Journal: Genome biology (2006)

Abstract Background This paper describes Pairagon+N-SCAN_EST, a gene annotation pipeline that uses only native alignments. For each expressed sequence it chooses the best genomic alignment. Systems like ENSEMBL and ExoGean rely on trans alignments, in which expressed sequences are aligned to the genomic loci of putative homologs. Trans alignments contain a high proportion of mismatches, gaps, and/or apparently unspliceable introns, compared to alignments of cDNA sequences to their native loci. The Pairagon+N-SCAN_EST pipeline's first stage is Pairagon, a cDNA-to-genome alignment program based on a PairHMM probability model. This model relies on prior knowledge, such as the fact that introns must begin with GT, GC, or AT and end with AG or AC. It produces very precise alignments of high quality cDNA sequences. In the genomic regions between Pairagon's cDNA alignments, the pipeline combines EST alignments with de novo gene prediction by using N-SCAN_EST. N-SCAN_EST is based on a generalized HMM probability model augmented with a phylogenetic conservation model and EST alignments. It can predict complete transcripts by extending or merging EST alignments, but it can also predict genes in regions without EST alignments. Because they are based on probability models, both Pairagon and N-SCAN_EST can be trained automatically for new genomes and data sets. Results On the ENCODE regions of the human genome, Pairagon+N-SCAN_EST was as accurate as any other system tested in the EGASP assessment, including ENSEMBL and ExoGean. Conclusion With sufficient mRNA/EST evidence, genome annotation without trans alignments can compete successfully with systems like ENSEMBL and ExoGean, which use trans alignments.
Genetic determinants of C-reactive protein in COPD
Authors: C. P. Hersh, D. T. Miller, D. J. Kwiatkowski, E. K. Silverman
Journal: European Respiratory Journal (2006)

Chronic obstructive pulmonary disease (COPD) is associated with a systemic inflammatory state, marked by elevations in serum inflammatory markers including C-reactive protein (CRP). The present study sought to determine epidemiological predictors of CRP levels, to estimate the genetic influence on CRP levels, and to identify genetic variants that affect CRP in a family-based study of COPD. CRP was measured by a high-sensitivity assay in participants from the Boston Early-Onset COPD Study. Predictors of CRP level were determined using multilevel linear models. Variance component analysis was used to estimate heritability and to perform genome-wide linkage analysis for CRP levels. Two variants in the surfactant protein B ( SFTPB ) gene were tested for association with CRP levels. Increased age, female sex, higher body mass index, greater smoking pack-yrs and reduced forced expiratory volume in one second were all associated with increased CRP levels. There was a significant genetic influence on CRP (heritability = 0.25). Genome-wide linkage analysis revealed several potentially interesting chromosomal regions, though no significant evidence for linkage was found. A short tandem repeat marker near SFTPB was significantly associated with CRP levels. There is a genetic influence on C-reactive protein levels in chronic obstructive pulmonary disease patients. Preliminary evidence suggests an association of the surfactant protein B gene with systemic inflammation in chronic obstructive pulmonary disease.