tbuckley/cabot-search huggingface dataset:
Clinicopathological and genotypic aspects of anticonvulsant-induced pseudolymphoma syndrome
Authors: T.S. Choi, K.S. Doh, S.H. Kim, M.S. Jang, K.S. Suh, S.T. Kim
Journal: British Journal of Dermatology (2003)

Pseudolymphoma syndrome (PLS) is relatively rare but can lead to death if there are extensive skin lesions, severe hepatitis, agranulocytosis and neutropenia. PLS may also give rise to harmful effects if misdiagnosed as malignant lymphoma and patients with PLS are treated unnecessarily with chemotherapy, because it may mimic histologically other lymphomas, including mycosis fungoides (MF).To examine the clinicopathological and genotypic features of anticonvulsant-induced PLS. Patients and methods We retrospectively reviewed clinical, laboratory and histological findings for eight cases of anticonvulsant-induced PLS, and performed T-cell receptor gene rearrangement using polymerase chain reaction with paraffin-embedded specimens from each case.The causative agents were carbamazepine (four cases), phenytoin (two cases), phenobarbital (one case) and valproic acid (one case). A cross-reaction between phenobarbital and phenytoin was observed in one case. The duration from the start of anticonvulsant therapy to skin eruption was 3-24 weeks (mean 7 weeks). The skin lesions were generalized maculopapular eruptions in all cases, including one case accompanied by vesiculopustular lesions. The frequencies of the associated features were as follows: facial oedema (88%), fever (75%), lymphadenopathy (63%), and hepatomegaly (25%). Laboratory findings revealed leukocytosis, atypical lymphocytes, eosinophilia, monocytosis, neutrophilia, lymphocytosis and abnormal liver function. Histopathologically, there was similarity between PLS and MF in that epidermotrophism of atypical lymphocytes (100%) and Pautrier's microabscess-like structures (38%) were observed. However, PLS has some differences from MF that include moderate to marked spongiosis (75%), necrotic keratinocytes (63%), and infiltration of eosinophils (25%) in the epidermis and, in the dermis, papillary dermal oedema (100%), extravasated erythrocytes (100%), lymphocytes within the dermis larger than those within the epidermis (63%), and infiltration of various inflammatory cells including neutrophils (50%). Genotypic analysis demonstrated a rearrangement of the T-cell receptor-gamma gene in one of eight cases studied. There were no deaths and all cases were improved at 2-9 weeks (mean 6 weeks), after the cessation of causative agents, systemic and topical corticosteroid therapy, and symptomatic therapy. There were no significant differences in clinical, laboratory and histological findings between the causative agents.PLS may show histopathological findings similar to MF and take a prolonged course even after the cessation of causative agents. Thus, a clear understanding and diagnosis of this disease is considered to have an important effect on treatment and prognosis.
Postinflammatory elastolysis and cutis laxa
Authors: Philip G. Lewis, Antoinette F. Hood, Nancy K. Barnett, Karen A. Holbrook
Journal: Journal of the American Academy of Dermatology (1990)

One of the rarest forms of cutis laxa is postinflammatory elastolysis and cutis laxa, a disease previously reported only in children in Africa and South America. This disease is characterized by an urticarial or papular eruption followed by acute destruction of elastic tissue that results in atrophy and severe disfigurement. It is distinguished from anetoderma and acquired cutis laxa by its clinical features, its occurrence in young children, and its relatively benign course. This article describes the first case of postinflarnmatory elastolysis and cutis laxa reported in a white child from North America.
Granzyme K: a novel mediator in acute airway inflammation
Authors: K Bratke, A Klug, P Julius, M Kuepper, M Lommatzsch, G Sparmann, W Luttmann, J C Virchow
Journal: Thorax (2008)

Granzymes are a subfamily of serine proteases involved in the pathogenesis of many inflammatory disorders. In contrast with granzyme A and B, the role of granzyme K (GrK) in human lung diseases is unknown. Therefore, the release and expression of GrK in allergic asthma, chronic obstructive pulmonary disease (COPD) and bronchopneumonia were investigated.Soluble GrK was quantified using an enzyme linked immunosorbent assay in the bronchoalveolar lavage fluid of patients with allergic asthma (before and after segmental allergen challenge), and in patients with mild COPD, pneumonia and in healthy controls. The molecular form of GrK was analysed by western blot. Flow cytometry was performed to determine the cellular expression of GrK.Compared with healthy controls, there were normal levels of soluble GrK in the bronchoalveolar lavage fluid of patients with COPD, and patients with allergic asthma before allergen challenge. In contrast, soluble GrK was strongly increased in the bronchoalveolar lavage fluid of patients with acute bronchopneumonia. In patients with allergic asthma, there was a significant increase in soluble GrK as well as in GrK expressing CD8(+) T cells in the bronchoalveolar lavage fluid 24 h and 72 h after allergen challenge. After allergen challenge, soluble GrK correlated with the percentage of GrK expressing CD8(+) T cells. Finally, it was shown that the endobronchial release of the CCR5 ligand CCL3 might be a mechanism for the recruitment of GrK(+)CD8(+) T cells after allergen challenge.These data provide the first evidence that expression of GrK is upregulated in acute airway inflammation, both in infectious and non-infectious diseases.
Effect of Intracoronary γ-Radiation Therapy on In-Stent Restenosis
Authors: Gary S. Mintz, Neil J. Weissman, Paul S. Teirstein, Steven G. Ellis, Ron Waksman, Robert J. Russo, Issam Moussa, Prabhaker Tripuraneni, Shrish Jani, Yoshio Kobayashi, Joseph A. Giorgianni, Chrysoula Pappas, Richard A. Kuntz, Jeffrey Moses, Martin B. Leon
Journal: Circulation (2000)

The aim of this study was to use serial volumetric intravascular ultrasound to evaluate the effect of gamma-radiation on recurrent in-stent restenosis.After successful reintervention, patients were randomized to receive either (192)Ir or placebo. Intravascular ultrasound studies with motorized pullback (0.5 mm/s) were performed immediately after irradiation and at 8-month follow-up in 70 patients. Paired volumetric analysis of the stented segment and of 5-mm proximal and distal reference segments was performed; this included measurements of the external elastic membrane, lumen, plaque and media (external elastic membrane minus lumen), stent, and intimal hyperplasia (stent minus lumen). Baseline proximal reference, stent, and distal reference measurements were similar in both groups. The changes in proximal and distal reference measurements of the external elastic membrane, plaque and media, and lumen areas were similar in both groups. However, the decrease in stented segment lumen volume was less in the (192)Ir patients than the placebo patients (-25+/-34 mm(3) versus -48+/-42 mm(3); P:=0.0225), and the increase in the volume of intimal hyperplasia in the stented segment was less in the (192)Ir patients than in the placebo patients (28+/-37 mm(3) versus 50+/-40 mm(3); P:=0.0352). When averaged over the length of the stented segment (32+/-13 mm versus 33+/-14 mm; P:=0.9), the increase in mean area of intimal hyperplasia was 0.8+/-1.0 mm(2) in the (192)Ir group and 1.6+/-1.2 mm(2) in the control group (P:=0.0065). Late stent-vessel wall malapposition was noted in one placebo patient and no (192)Ir patients.gamma-Radiation therapy can effectively prevent recurrent in-stent restenosis by inhibiting neointimal formation within the stent. At the stent edge, there were no significant differences between (192)Ir and placebo patients.
Tumor Microenvironment–Derived Proteins Dominate the Plasma Proteome Response during Breast Cancer Induction and Progression
Authors: Sharon J. Pitteri, Karen S. Kelly-Spratt, Kay E. Gurley, Jacob Kennedy, Tina Busald Buson, Alice Chin, Hong Wang, Qing Zhang, Chee-Hong Wong, Lewis A. Chodosh, Peter S. Nelson, Samir M. Hanash, Christopher J. Kemp
Journal: Cancer Research (2011)

Abstract Tumor development relies upon essential contributions from the tumor microenvironment and host immune alterations. These contributions may inform the plasma proteome in a manner that could be exploited for cancer diagnosis and prognosis. In this study, we employed a systems biology approach to characterize the plasma proteome response in the inducible HER2/neu mouse model of breast cancer during tumor induction, progression, and regression. Mass spectrometry data derived from approximately 1.6 million spectra identified protein networks involved in wound healing, microenvironment, and metabolism that coordinately changed during tumor development. The observed alterations developed prior to cancer detection, increased progressively with tumor growth and reverted toward baseline with tumor regression. Gene expression and immunohistochemical analyses suggested that the cancer-associated plasma proteome was derived from transcriptional responses in the noncancerous host tissues as well as the developing tumor. The proteomic signature was distinct from a nonspecific response to inflammation. Overall, the developing tumor simultaneously engaged a number of innate physiologic processes, including wound repair, immune response, coagulation and complement cascades, tissue remodeling, and metabolic homeostasis that were all detectable in plasma. Our findings offer an integrated view of tumor development relevant to plasma-based strategies to detect and diagnose cancer. Cancer Res; 71(15); 5090–100. ©2011 AACR.
Bronchial aspirin challenge causes specific eicosanoid response in aspirin-sensitive asthmatics.
Authors: A Szczeklik, K Sladek, R Dworski, E Nizankowska, J Soja, J Sheller, J Oates
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

We have shown that inhalation of lysine aspirin enhances leukotriene production in the lungs of patients with aspirin-induced asthma (AIA). To assess the specificity of this reaction, we compared two well-matched groups of patients: eleven with AIA versus 14 asthmatics tolerant to aspirin (ATA). All subjects underwent bronchoalveolar lavage (BAL) with saline followed immediately by instillation of 10 mg of lysine aspirin, into a right middle lobe segmental bronchus, which was lavaged 15 min later. At baseline the two groups did not differ with respect to BAL fluid concentrations of cyclooxygenase products, peptido-leukotrienes, histamine, tryptase, interleukin-5 (IL-5), eosinophil cationic protein (ECP), or eosinophil number. Fifteen minutes after aspirin instillation, there was a statistically significant rise in peptido-leukotrienes, IL-5, and eosinophil number in AIA, but not in ATA, but not in ATA patients. In the former, but not in the latter group, mean histamine concentrations rose in response to aspirin, approaching the level of statistical significance. Tryptase and ECP levels showed no significant change. Aspirin significantly depressed PGE2 and thromboxane B2 (TXB2) in both groups, however PGD2, PGF2 alpha, and 9 alpha, 11 beta-PGF2 decreased only in ATA patients. A characteristic disturbance in eicosanoid balance, produced by aspirin in patients intolerant to this drug, might explain precipitation of asthma attacks.
Human syndromes of immunodeficiency and dysregulation are characterized by distinct defects in T-cell receptor repertoire development
Authors: Xiaomin Yu, Jorge R. Almeida, Sam Darko, Mirjam van der Burg, Suk See DeRavin, Harry Malech, Andrew Gennery, Ivan Chinn, Mary Louise Markert, Daniel C. Douek, Joshua D. Milner
Journal: Journal of Allergy and Clinical Immunology (2014)
Control of rat natural killer cell-mediated allorecognition by a major histocompatibility complex region encoding nonclassical class I antigens.
Authors: J T Vaage, C Naper, G Løvik, D Lambracht, A Rehm, H J Hedrich, K Wonigeit, B Rolstad
Journal: The Journal of Experimental Medicine (1994)

The ability of natural killer (NK) cells to eliminate normal allogeneic hemic cells is well established in several species including mice, rats, and humans. The controlling elements for NK susceptibility in these species map to the major histocompatibility complex (MHC), but in contrast to findings in mice and humans, the mode of inheritance is not always recessive in rats. This finding is not easily explained by the missing self and hemopoietic histocompatibility (Hh) models for NK recognition, and has led to the idea that certain alloantigens may trigger NK cell reactivity. In our in vitro system for assessing rat NK alloreactivity, we have employed target and inhibitor cells from a large panel of MHC congenic, intra-MHC recombinant and MHC mutant rat strains, as well as appropriate F1 hybrids between them, and we show the following: (a) The nonclassical class I (RT1.C) region was most important in determining the susceptibility of target cells to alloreactive NK cells in vitro. Lymphocyte susceptibility to lysis in vivo also mapped to the C region, which supports the concept that the in vivo and in vitro alloreactivity assays reflect the same recognition process. (b) Four different RT1-controlled NK allospecificities (represented by the u, l, a, and n haplotypes) could be discerned when we used polyclonal NK cells from the PVG (RT1c) strain as effector cells. Three of the target specificities recognized were controlled mainly by the RT1.C region. (c) The expression of RT1.C region-controlled parental strain NK allodeterminants could be demonstrated in F1 hybrids heterozygous for the C region alone and were therefore inherited nonrecessively. (d) Loss of an RT1.C region-controlled NK allospecificity could be shown with the MHC mutant LEW.1LM1 rat strain characterized by a genomic deletion of about 100 kb of the C region. Taken together, these observations have demonstrated a major importance of the nonclassical class I region, i.e., RT1.C, in controlling rat NK allorecognition, and have thereby assigned a hitherto undescribed immunological property to this region. Furthermore, some of the present data are consistent with the existence of polymorphic NK-triggering alloantigens that are coded for by the RT1.C region.
Bazedoxifene Exhibits Antiestrogenic Activity in Animal Models of Tamoxifen-Resistant Breast Cancer: Implications for Treatment of Advanced Disease
Authors: Suzanne E. Wardell, Erik R. Nelson, Christina A. Chao, Donald P. McDonnell
Journal: Clinical Cancer Research (2013)

There is compelling evidence to suggest that drugs that function as pure estrogen receptor (ER-α) antagonists, or that downregulate the expression of ER-α, would have clinical use in the treatment of advanced tamoxifen- and aromatase-resistant breast cancer. Although such compounds are currently in development, we reasoned, based on our understanding of ER-α pharmacology, that there may already exist among the most recently developed selective estrogen receptor modulators (SERM) compounds that would have usage as breast cancer therapeutics. Thus, our objective was to identify among available SERMs those with unique pharmacologic activities and to evaluate their potential clinical use with predictive models of advanced breast cancer.A validated molecular profiling technology was used to classify clinically relevant SERMs based on their impact on ER-α conformation. The functional consequences of these observed mechanistic differences on (i) gene expression, (ii) receptor stability, and (iii) activity in cellular and animal models of advanced endocrine-resistant breast cancer were assessed.The high-affinity SERM bazedoxifene was shown to function as a pure ER-α antagonist in cellular models of breast cancer and effectively inhibited the growth of both tamoxifen-sensitive and -resistant breast tumor xenografts. Interestingly, bazedoxifene induced a unique conformational change in ER-α that resulted in its proteasomal degradation, although the latter activity was dispensable for its antagonist efficacy.Bazedoxifene was recently approved for use in the European Union for the treatment of osteoporosis and thus may represent a near-term therapeutic option for patients with advanced breast cancer.
Sputum induction in children
Authors: None Leader of the Working Group:, P.G. Gibson, None Members of the Working Group:, D.C. Grootendorst, R. Henry, I. Pin, P.L. Rytila, P. Wark, N. Wilson, R. Djukanovic
Journal: European Respiratory Journal (2002)

Sputum induction has been used to study asthma in children since the first description of the technique in 1992 1. Since then, >20 reports (five reviews) have appeared in the literature describing sputum induction in children with airways disease. In general, sputum induction in children of >6 yrs is safe and has a satisfactory success rate.

Approximately 500 children have been studied by sputum induction. The diagnoses of the studied children include stable asthma (n=308), acute asthma (n=18) and healthy control subjects (n=185). Studies have included children aged 5–18 yrs, with a mean age of 11.2 yrs. Most studies have included children of >6 yrs. Studies of children with asthma have included subjects across the spectrum of severity.

The following issues regarding sputum induction in children are reviewed in the present article: 1) protocols used in children; 2) safety of induction; 3) management of airway obstruction during sputum induction; 4) sputum processing; 5) normal values in children; 6) findings in asthmatic children; 7) effect of treatment on induced sputum parameters; and 8) clinical applications.

A wide variety of sputum induction protocols have been reported successful in children (table 1⇓). There is great variation as to the brands of nebuliser used. All of the studies have used ultrasonic nebulisers, but these were either high­ or low­output devices. Hypertonic saline has been used either at 4.5% (in four studies) or by increasing concentrations from 3 to 4 and then …
Contribution of Clinical Correlates and 13 C-Reactive Protein Gene Polymorphisms to Interindividual Variability in Serum C-Reactive Protein Level
Authors: Sekar Kathiresan, Martin G. Larson, Ramachandran S. Vasan, Chao-Yu Guo, Philimon Gona, John F. Keaney, Peter W.F. Wilson, Christopher Newton-Cheh, Stacy L. Musone, Amy L. Camargo, Jared A. Drake, Daniel Levy, Christopher J. O’Donnell, Joel N. Hirschhorn, Emelia J. Benjamin
Journal: Circulation (2006)

Serum C-reactive protein (CRP) level is a heritable complex trait that predicts incident cardiovascular disease. We investigated the clinical and genetic sources of interindividual variability in serum CRP.We studied serum CRP in 3301 Framingham Heart Study (FHS) participants (mean age 61 years, 53% women). Twelve clinical covariates explained 26% of the variability in CRP level, with body mass index alone explaining 15% (P<0.0001) of the variance. To investigate the influence of genetic variation at the CRP gene on CRP levels, we first constructed a dense linkage disequilibrium map for common single-nucleotide polymorphisms (SNPs) spanning the CRP locus (1 SNP every 850 bases, 26 kilobase [kb] genomic region). Thirteen CRP SNPs were genotyped in 1640 unrelated FHS participants with measured CRP levels. After adjustment for clinical covariates, 9 of 13 SNPs were associated with CRP level (P<0.05). To account for correlation among SNPs, we conducted forward stepwise selection among all 13 SNPs; a triallelic SNP (rs3091244) remained associated with CRP level (stepwise P<0.0001). The triallelic SNP (C-->T-->A; allele frequencies 62%, 31%, and 7%), located in the promoter sequence, explained 1.4% of total serum CRP variation; haplotypes harboring the minor T and A alleles of this SNP were associated with higher CRP level (haplotype P=0.0002 and 0.004).In our community-based sample, clinical variables explained 26% of the interindividual variation in CRP, whereas a common triallelic CRP SNP contributed modestly. Studies of larger samples are warranted to assess the association of genetic variation in CRP and risk of cardiovascular disease.
“Edge Effect” of <sup>32</sup> P Radioactive Stents Is Caused by the Combination of Chronic Stent Injury and Radioactive Dose Falloff
Authors: Willem J. van der Giessen, Evelyn Regar, Miranda S. Harteveld, Veronique L.M.A. Coen, Rohit Bhagwandien, Arthur Au, Peter C. Levendag, Jurgen Ligthart, Patrick W. Serruys, Ad den Boer, Pieter D. Verdouw, Eric Boersma, Ty Hu, Heleen M.M. van Beusekom
Journal: Circulation (2001)

Background Radioactive stents have been reported to reduce in-stent neointimal thickening. An unexpected increase in neointimal response was observed, however, at the stent-to-artery transitions, the so-called “edge effect.” To investigate the factors involved in this edge effect, we studied stents with 1 radioactive half and 1 regular nonradioactive half, thereby creating a midstent radioactive dose-falloff zone next to a nonradioactive stent-artery transition at one side and a radioactive stent-artery transition at the other side. Methods and Results Half-radioactive stents (n=20) and nonradioactive control stents (n=10) were implanted in the coronary arteries of Yucatan micropigs. Animals received aspirin and clopidogrel as antithrombotics. After 4 weeks, a significant midstent stenosis was observed by angiography in the half-radioactive stents. Two animals died suddenly because of coronary occlusion at this mid zone at 8 and 10 weeks. At 12-week follow-up angiography, intravascular ultrasound and histomorphometry showed a significant neointimal thickening at the midstent dose-falloff zone of the half-radioactive stents, but not at the stent-to-artery transitions at both extremities. Such a midstent response (mean angiographic late loss 1.0 mm) was not observed in the nonradioactive stents (mean loss 0.4 to 0.6 mm; P &lt; 0.01). Conclusions The edge effect of high-dose radioactive stents in porcine coronary arteries is associated with the combination of stent injury and radioactive dose falloff.
Foxp3<sup>+</sup>Helios<sup>+</sup>regulatory T cells are expanded in active systemic lupus erythematosus
Authors: Tobias Alexander, Arne Sattler, Lars Templin, Siegfried Kohler, Christian Groß, Andreas Meisel, Birgit Sawitzki, Gerd-Rüdiger Burmester, Renate Arnold, Andreas Radbruch, Andreas Thiel, Falk Hiepe
Journal: Annals of the Rheumatic Diseases (2012)

Objectives Recent data debate the suitability of Helios, an Ikaros family member, as a marker for thymic-derived regulatory T cells (Treg). Nevertheless, Foxp3+ Helios+ Treg may be of particular relevance in mediating immune tolerance in chronic autoimmunity, such as systemic lupus erythematosus (SLE), as they possess enhanced suppressive function, compared to Foxp3+ Helios− Treg. Methods Multicolour flow cytometry was performed to analyse Foxp3 and Helios expression in peripheral blood CD4 T cells from SLE patients, compared to healthy controls (HC) and systemic sclerosis (SSc) and rheumatoid arthritis (RA) patients. Cytokine production, chemokine receptor expression for CXCR3 and CCR4, basal signal transducer and activator of transcription 5 (STAT5)a phosphorylation levels and T-cell receptor (TCR) Vβ repertoire were analysed by flow cytometry, and the methylation status of the Foxp3 locus (Treg-specific demethylated region, TSDR) by real-time PCR. Results Frequencies of Foxp3+ Helios+ Treg, unlike Foxp3+ Helios− T cells, were significantly increased in SLE patients and positively correlated with disease activity, whereas they were unaltered in SSc and RA patients. Compared to HC, Foxp3+ Helios+ Treg in SLE predominantly displayed a CD45RA−/CD31−/FoxP3low memory phenotype with increased Ki-67 expression, enhanced basal pSTAT5a levels and a restricted TCR repertoire. Nonetheless, similar to HC, Foxp3+ Helios+ Treg in SLE lacked effector cytokine production, possessed a highly demethylated TSDR and expressed comparable levels of CXCR3 and CCR4. Conclusions Our data suggest that Helios-expressing Foxp3+ Treg with functional suppressive capacity and migratory potential into inflamed tissues are expanded in active SLE, presumably through γ-chain signalling cytokines and TCR stimulation, to compensate for autoreactive effector responses.