tbuckley/cabot-search huggingface dataset:
Genetic predisposition and pathogenetic mechanisms of interstitial lung diseases of unknown origin
Authors: G M Verleden, R M du Bois, D Bouros, M Drent, A Millar, J Müller-Quernheim, G Semenzato, S Johnson, G Sourvino, D Olivier, A Pietinalho, A Xaubet
Journal: European Respiratory Journal (2001)

Understanding of the cellular and cytokine interactions associated with inflammation and fibrosis in interstitial lung diseases (ILDs) has increased substantially during the past few years. Presently, many agents are known to have the ability to induce ILDs, although only a small percentage of exposed individuals will develop the disease. In addition, the majority of ILDs are of unknown origin and many are labelled “idiopathic”. Therefore, host susceptibility, genetic factors and, possibly, environmental cofactors may be important for the clinical expression of ILDs. The present review reports evidence of the genetic predisposition to develop ILDs of unknown origin, more specifically sarcoidosis, idiopathic pulmonary fibrosis (IPF), lymphangioleio-myomatosis and ILDs, in systemic sclerosis. For instance, for sarcoidosis and IPF several histocompatibility antigens have been associated with the development and/or the clinical presentation of the disease. Furthermore, there are also several types of ILD that are associated with inherited disorders, of which the tuberous sclerosis complex is only one example. This clearly indicates that pulmonary fibrosis can be influenced by genetic factors. Familial occurrence of sarcoidosis and IPF is also well known, although the exact modes of inheritance are debatable. Several studies have shown that extrinsic factors, such as single or multiple fibrosing agents, probably contribute to the development of clinical ILDs of unknown origin. It is probable that some of these studies deal with patients who do not have classical IPF, as recently defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) consensus. Therefore, the true role of these extrinsic factors in the development of IPF, or even sarcoidosis, remains speculative. With the help of animal studies and, more specifically, by using knock-out mice, it may be possible in the near future to unravel at least some of the genes that are responsible for the increased susceptibility of the development of interstitial lung diseases.
Intracoronary Bone Marrow Cell Transfer After Myocardial Infarction
Authors: Gerd P. Meyer, Kai C. Wollert, Joachim Lotz, Jan Steffens, Peter Lippolt, Stephanie Fichtner, Hartmut Hecker, Arnd Schaefer, Lubomir Arseniev, Bernd Hertenstein, Arnold Ganser, Helmut Drexler
Journal: Circulation (2006)

Intracoronary transfer of autologous bone marrow cells (BMCs) may enhance recovery of left ventricular (LV) function in patients after acute myocardial infarction (AMI). However, clinical studies addressing the effects of BMCs after AMI have covered only limited time frames ranging from 3 to 6 months. The critical question of whether BMC transfer can have a sustained impact on LV function remains unanswered.After percutaneous coronary intervention with stent implantation (PCI) of the infarct-related artery, 60 patients were randomized 1:1 to a control group with optimal postinfarction therapy and a BMC transfer group that also received an intracoronary BMC infusion 4.8+/-1.3 days after PCI. Cardiac MRI was performed 3.5+/-1.5 days, 6+/-1 months, and 18+/-6 months after PCI. BMC transfer was not associated with adverse clinical events. In the control group, mean global LV ejection fraction increased by 0.7 and 3.1 percentage points after 6 and 18 months, respectively. LV ejection fraction in the BMC transfer group increased by 6.7 and 5.9 percentage points. The difference in LVEF improvement between groups was significant after 6 months but not after 18 months (P=0.27). The speed of LV ejection fraction recovery over the course of 18 months was significantly higher in the BMC transfer group (P=0.001).In this study, a single dose of intracoronary BMCs did not provide long-term benefit on LV systolic function after AMI compared with a randomized control group; however, the study suggests an acceleration of LV ejection fraction recovery after AMI by BMC therapy.
Idiopathic chronic cough: association with organ specific autoimmune disease and bronchoalveolar lymphocytosis
Authors: S S Birring
Journal: Thorax (2003)

We have recently reported a strong association between organ specific autoimmune disease and idiopathic chronic cough and have suggested that cough may be caused by airway inflammation secondary to aberrant homing of activated lymphocytes to the lung. An immunopathological study was undertaken to test the hypothesis that idiopathic chronic cough is associated with lymphocytic airway inflammation.Bronchoscopy, bronchial biopsies, bronchoalveolar lavage (BAL), and peripheral blood and BAL flow cytometry were performed in 19 patients with idiopathic chronic cough, 14 with explained chronic cough, and 11 normal subjects.Organ specific autoimmune disease or positive autoantibodies were present in eight of the 19 patients with idiopathic cough, in one of the 14 patients with explained cough, and in one of the 11 normal subjects. Median BAL fluid differential lymphyocyte counts were significantly higher in patients with idiopathic cough (10.0%) than in normal subjects (6.3%, 95% confidence interval of difference 1.5 to 11.9, p = 0.01) or patients with explained cough (5.2%, 95% CI of difference 2.0 to 10.4, p = 0.001). There were no differences in bronchial biopsy T lymphocyte counts between the groups. The mean (SE) proportion of CD3+ peripheral blood mononuclear cells expressing CD4 was significantly higher in normal subjects than in patients with idiopathic cough (69 (3)% v 58 (3)%, mean difference 11%, 95% CI of difference 2 to 20, p<0.02) but not than those with explained chronic cough (63 (2)%). There were no differences in BAL T lymphocyte phenotype between groups.BAL fluid lymphocytosis occurs in some patients with idiopathic chronic cough. The association of idiopathic chronic cough with organ specific autoimmune disease raises the possibility that this might be caused by lymphocyte homing from the primary site of autoimmune inflammation or the result of an autoimmune process in the lung.
Circulating and Dietary <i>Trans</i> Fatty Acids and Incident Type 2 Diabetes in Older Adults: The Cardiovascular Health Study
Authors: Qianyi Wang, Fumiaki Imamura, Wenjie Ma, Molin Wang, Rozenn N. Lemaitre, Irena B. King, Xiaoling Song, Mary L. Biggs, Joseph A. Delaney, Kenneth J. Mukamal, Luc Djousse, David S. Siscovick, Dariush Mozaffarian
Journal: Diabetes Care (2015)

OBJECTIVE To investigate the effects of trans fatty acids (TFAs) on type 2 diabetes mellitus (DM) by specific TFA subtype or method of assessment. RESEARCH DESIGN AND METHODS In the Cardiovascular Health Study, plasma phospholipid trans (t)-16:1n9, t-18:1, and cis (c)/t-, t/c-, and t/t-18:2 were measured in blood drawn from 2,919 adults aged 74 ± 5 years and free of prevalent DM in 1992. Dietary TFA was estimated among 4,207 adults free of prevalent DM when dietary questionnaires were initially administered in 1989 or 1996. Incident DM was defined through 2010 by medication use or blood glucose levels. Risks were assessed by Cox proportional hazards. RESULTS In biomarker analyses, 287 DM cases occurred during 30,825 person-years. Both t-16:1n9 (extreme quartile hazard ratio 1.59 [95% CI 1.04–2.42], P-trend = 0.04) and t-18:1 (1.91 [1.20–3.03], P-trend = 0.01) levels were associated with higher incident DM after adjustment for de novo lipogenesis fatty acids. In dietary analyses, 407 DM cases occurred during 50,105 person-years. Incident DM was positively associated with consumption of total TFAs (1.38 [1.03–1.86], P-trend = 0.02), t-18:1 (1.32 [1.00–1.76], P-trend = 0.04), and t-18:2 (1.41 [1.05–1.89], P-trend = 0.02). After further adjustment for other dietary habits, however, the associations of estimated dietary TFA with DM were attenuated, and only nonsignificant positive trends remained. CONCLUSIONS Among older adults, plasma phospholipid t-16:1n9 and t-18:1 levels were positively related to DM after adjustment for de novo lipogenesis fatty acids. Estimated dietary TFA was not significantly associated with DM. These findings highlight the need for further observational, interventional, and experimental studies of the effects TFA on DM.
Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study
Authors: Chang Kim Hyeon, Mo Nam Chung, Ha Jee Sun, Hyub Han Kwang, Dae Kyu Oh, Il Suh
Journal: BMJ (2004)

To examine the relation between the normal range of serum aminotransferase concentration and mortality from liver disease.Prospective cohort study.Korea Medical Insurance Corporation study with eight years' follow up.94,533 men and 47,522 women aged 35-59 years.Mortality from liver diseases according to death certificate.There was a positive association between the aminotransferase concentration, even within normal range (35-40 IU/l), and mortality from liver disease. Compared with the concentration < 20 IU/l, the adjusted relative risks for an aspartate aminotransferase concentration of 20-29 IU/l and 30-39 IU/l were 2.5 (95% confidence interval 2.0 to 3.0) and 8.0 (6.6 to 9.8) in men and 3.3 (1.7 to 6.4) and 18.2 (8.1 to 40.4) in women, respectively, The corresponding risks for alanine aminotransferase were 2.9 (2.4 to 3.5) and 9.5 (7.9 to 11.5) in men and 3.8 (1.9 to 7.7) and 6.6 (1.5 to 25.6) in women, respectively. According to receiver operating characteristic curves the best cut-off values for the prediction of liver disease in men were 31 IU/l for aspartate aminotransferase and 30 IU/l for alanine aminotransferase.People with slightly increased aminotransferase activity, but still within the normal range, should be closely observed and further investigated for liver diseases.
Mannosylated Lipid Nano-emulsions Loaded with Lycorine-oleic Acid Ionic Complex for Tumor Cell-specific Delivery
Authors: Yangming Guo, Xing Liu, Xun Sun, Qiang Zhang, Tao Gong, Zhirong Zhang
Journal: Theranostics (2012)

This study was to prepare a mannosylated lycorine lipid nano-emulsion formulation (M-LYC-OA-LNEs) for the aim of achieving tumor targeting delivery of lycorine (LYC) .The low lipophilicity of LYC made it hard to be dispersed into lipid nano-emulsions (LNEs).In order to increase its lipophilicity, lycorine-oleic acid ionic complex (LYC-OA) was made.M-LYC-OA-LNEs and uncoated lycorine-oleic acid loaded lipid nano-emulsions (LYC-OA-LNEs) were prepared by solvent injection method and characterized by transmission electron microscopy (TEM), particle size, polydispersity index, zeta-potential and entrapment efficiency analysis.The in vitro cellular uptake and growth inhibition activity studies were performed on A549 cell lines.The entrapment efficiency of M-LYC-OA-LNEs was 82.7 ± 1.6 %.The cellular uptake study showed that coated LNEs were preferably taken up by A549 cells than uncoated LNEs.The effective test by MTT assay showed better growth inhibition activity of M-LYC-OA-LNEs on A549 cell lines when compared with LYC-OA-LNEs and blank LNEs.These results demonstrated that M-LYC-OA-LNEs could be a promising formulation for tumor targeting delivery of LYC with the potential of being applied in the diagnosis and treatment of cancer.
Evidence of Gene—Gene Interactions in the Genetic Susceptibility to Renal Impairment after Unilateral Nephrectomy
Authors: MASAHIDE SHIOZAWA, ABRAHAM P. PROVOOST, RICHARD P. E. VAN DOKKUM, REBECCA R. MAJEWSKI, HOWARD J. JACOB
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The number of patients with hypertension-associated end-stage renal failure (ESRF) continues to increase despite improved antihypertensive management and early detection programs. Variation for the development of renal complications in hypertension may reflect independent genetic susceptibility to ESRF. The genetically hypertensive fawn-hooded rat is characterized by the early presence of systolic hypertension, glomerular hypertension, progressive proteinuria (UPV), and focal glomerulosclerosis (FGS), resulting in premature death as a result of renal failure. In the present study, the genetic basis of hypertension-associated ESRF in an F2 intercross consisting of 337 animals, in which systolic BP, UPV, albuminuria, and FGS, were studied at 8 wk after a unilateral nephrectomy performed at 5 to 6 wk of age. A total genome scan, consisting of 418 markers, was used to identify regions that contribute to the pathogenesis of UPV and FGS. Linkage analysis revealed five loci involved in the development of renal impairment. Of these five, two ( Rf-1, Rf-2 ) had been identified previously. There seems to be strong interactive effects between the various loci and their impact on UPV and the other parameters of renal impairment, as well as an interaction with BP. In particular, Rf-1 seems to play a major role in determining the severity of the disease. This study is the first to report the interaction of more than two loci to produce progressive renal failure, suggesting that the genetic dissection of renal failure in humans will require understanding of how multiple genes interact with each other and BP to produce ESRF.
Ruxolitinib‐induced reversal of alopecia universalis in a patient with essential thrombocythemia
Authors: Lisa Pieri, Paola Guglielmelli, Alessandro M. Vannucchi
Journal: American Journal of Hematology (2014)

Ruxolitinib is an inhibitor of activated JAK1 and JAK2 approved for the treatment of patients with myelofibrosis 1. Disregulated activation of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, caused by activating mutations of JAK2, myeloproliferative leukemia virus oncogene, the thrombopoietin receptor (MPL), and calreticulin (CALR), is implicated in the uncontrolled proliferation of hematopoietic progenitors and the generation of a proinflammatory reaction responsible for symptomatic burden 2. Ruxolitinib is under scrutiny in other hematologic and solid malignances as well as in rheumatoid arthritis and psoriasis. Recent data suggest that the list of autoimmune disorders in which ruxolitinib may be efficacious should include alopecia areata (AA) 3. It is assumed that the cytolytic damage to the hair follicle in AA is caused by autoreactive CD8+ T cells that expand and self-maintain through a cascade of cytokines including interferon gamma, interleukin-2 and -15; these cytokine's receptors signal through JAK1 and JAK2 (JAK1/JAK3 for interferon), therefore, they are inhibited by ruxolitinib 4. Topical administration of ruxolitinib promoted a full coat of hair in a mouse model of AA, and three individuals with AA receiving 20 mg ruxolitinib twice daily exhibited near-complete hair regrowth within 3–5 months 3. A 24-year old lady was diagnosed with essential thrombocythemia in 1992 because of sustained thrombocytosis (650 × 109/L) and consistent bone marrow biopsy. She remained untreated until 2006, when platelet count was 1,200 × 109/L and she complained of severe microvascular symptoms; at that time, she was found JAK2V617F mutated. We prescribed interferon-alpha, that was withdrawn soon for intolerance. She refused hydroxyurea and anagrelide on several occasions, notwithstanding severe complains. Finally, in 2009, she was enrolled in a phase II trial (NCT00726232) with ruxolitinib 5; she is still on therapy at 15 mg twice daily after 71 months with control of platelet count, complete resolution of symptoms, and no side effects. On March 2002, the patient had been diagnosed as suffering from AA, eventuating into alopecia universalis in 2006 with loss of eyelashes and eyebrows (Image 1A). Then, after 10 months of receiving ruxolitinib, she presented an undeniable improvement of alopecia with progressively extending areas of hair regrowth shortly leading to almost complete recovery, that is, durable at 50+ months (Image 1B). At the time of hair regrowth in the patient, we suspected an association with ruxolitinib administration, but could not substantiate it. After the seminal report of Xing et al., it is now clear that the remission of alopecia universalis was a highly desirable "side effect" of therapy in our patient receiving ruxolitinib for other reasons.
Epigenetic Therapy Using Belinostat for Patients With Unresectable Hepatocellular Carcinoma: A Multicenter Phase I/II Study With Biomarker and Pharmacokinetic Analysis of Tumors From Patients in the Mayo Phase II Consortium and the Cancer Therapeutics Research Group
Authors: Winnie Yeo, Hyun C. Chung, Stephen L. Chan, Ling Z. Wang, Robert Lim, Joel Picus, Michael Boyer, Frankie K.F. Mo, Jane Koh, Sun Y. Rha, Edwin P. Hui, Hei C. Jeung, Jae K. Roh, Simon C.H. Yu, Ka F. To, Qian Tao, Brigette B. Ma, Anthony W.H. Chan, Joanna H.M. Tong, Charles Erlichman, Anthony T.C. Chan, Boon C. Goh
Journal: Journal of Clinical Oncology (2012)

Epigenetic aberrations have been reported in hepatocellular carcinoma (HCC). In this study of patients with unresectable HCC and chronic liver disease, epigenetic therapy with the histone deacetylase inhibitor belinostat was assessed. The objectives were to determine dose-limiting toxicity and maximum-tolerated dose (MTD), to assess pharmacokinetics in phase I, and to assess activity of and explore potential biomarkers for response in phase II.
Antigen-pulsed dendritic cells can efficiently induce an antibody response in vivo.
Authors: T Sornasse, V Flamand, G De Becker, H Bazin, F Tielemans, K Thielemans, J Urbain, O Leo, M Moser
Journal: The Journal of Experimental Medicine (1992)

The aim of this study was to develop an immunization procedure avoiding external adjuvant. Data are presented showing that syngeneic dendritic cells (DC), which have been pulsed in vitro with antigen, induce a strong antibody response in mice. By contrast, antigen (Ag)-pulsed low-density B cells, although equally able to induce interleukin 2 secretion by an Ag-specific T cell hybridoma in vitro, only weakly prime the mice in vivo. Moreover, we show that the injection of Ag-pulsed DC induces the synthesis of isotypes similar to the immunoglobulin classes detected after immunization with the same Ag in complete Freund's adjuvant. Importantly, high amounts of IgG2a antibodies are produced, suggesting that T helper type 1 cells are activated. Collectively, these data indicate that DC can initiate a primary humoral response and that they may be used as physiological adjuvant in vivo.
CONCANAVALIN A BINDING PROTEINS OF LYMPHOID CELL SURFACE
Authors: Yong Sung Choi, James C. Jenson
Journal: The Journal of Experimental Medicine (1974)

A Concanavalin A binding protein of chicken lymphoid cells was isolated by affinity chromatography of intact lymphoid cells. This protein with a mol wt of 160,000 daltons revealed two peptides (30,000 and 20,000 daltons) in SDS-acrylamide gel electrophoresis.
Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial
Authors: Nick Thatcher, Fred R Hirsch, Alexander V Luft, Aleksandra Szczesna, Tudor E Ciuleanu, Mircea Dediu, Rodryg Ramlau, Rinat K Galiulin, Beatrix Bálint, György Losonczy, Andrzej Kazarnowicz, Keunchil Park, Christian Schumann, Martin Reck, Henrik Depenbrock, Shivani Nanda, Anamarija Kruljac-Letunic, Raffael Kurek, Luis Paz-Ares, Mark A Socinski
Journal: The Lancet Oncology (2015)
Angiogenic effects of sequential release of VEGF-A165 and PDGF-BB with alginate hydrogels after myocardial infarction
Authors: X HAO, E SILVA, A MANSSONBROBERG, K GRINNEMO, A SIDDIQUI, G DELLGREN, E WARDELL, L BRODIN, D MOONEY, C SYLVEN
Journal: Cardiovascular Research (2007)

Objective This study investigates whether local sequential delivery of vascular endothelial growth factor-A165 (VEGF-A165) followed by platelet-derived growth factor-BB (PDGF-BB) with alginate hydrogels could induce an angiogenic effect and functional improvement greater than single factors after myocardial infarction.
In a small multideterminant peptide, each determinant is recognized by a different V beta gene segment.
Authors: N K Nanda, K K Arzoo, E E Sercarz
Journal: The Journal of Experimental Medicine (1992)

Given the vast potential for diversification of the T cell receptor (TCR) repertoire and the fact that V(a) beta mice exist in the wild, it would have been predicted that in spite of the absence of 10 TCR V beta gene segments, V(a) beta mice would still have been able to produce an antigen-specific T cell response to all determinants. We have recently shown that Vb beta mice, with a wild-type TCR V beta repertoire, respond to peptide 110-121 of sperm whale myoglobin, with a majority of T cells expressing TCR V beta 8.2 and restricted to a hybrid I-A(d)/I-E(d) major histocompatibility complex molecule, and a smaller number of T cells expressing TCR V beta 8.1 and restricted to the I-A(d) molecule. However, V(a) beta mice, lacking members of the TCR V beta 8 gene family, responded only with I-A(d)-restricted T cells. Thus, it appeared that the I-A(d)-restricted response was less constrained, or more plastic. We now show that the two separate panels of I-A(d)-restricted T cell hybrids derived from V(a) beta or Vb beta mice in fact recognize distinct determinants within the same peptide 110-121. The determinant recognized by V(a) beta T cells is NH2 terminal (core: 110-118) with an absolute requirement for the residue Ala-110 for a successful interaction with TCRs. On the other hand, Vb beta T cells recognize the COOH-terminal region (core: 112-118) on the same peptide with an absolute requirement for COOH-terminal residue 118. In the dominance hierarchy displayed by the three distinct determinants of peptide 110-121, V(a) beta mice cannot recognize the two most dominant: the hybrid I-A(d)/I-E(d)-restricted determinant and the COOH-terminal, I-A(d)-restricted determinant. They instead respond with T cells specific for a third, distinctly NH2-terminal determinant. Our results show a strict association between recognition of a particular specificity and TCR V beta usage. This evidence suggests that even when a small peptide induces a heterogenous group of TCR V beta S, this need not be considered evidence for plasticity. Rather, at the level of individual determinants within the peptide, the results can point in the opposite direction, towards serious constraints in recognition at the level of V beta expression.
610 IgE antibodies cross-reaction between Der p1, the major allergen of Dermatophagoides pteronyssinus and Ananain, a cysteine proteinase from Ananas comosus, the pineapple plant
Authors: T MUSU, J RABILLON, B DAVID, J DANDEU, M GUINNEPAIN, Y LOOZE
Journal: Journal of Allergy and Clinical Immunology (1996)
Nuclear Factor-κB and Tumor-Associated Macrophages
Authors: Alessandra Mancino, Toby Lawrence
Journal: Clinical Cancer Research (2010)

Tumor-associated macrophages (TAM) have been linked with the progression of cancer by favoring tumor angiogenesis, growth, and metastasis. The precise mechanisms that maintain the protumor phenotype of TAM are poorly understood, but recent research has highlighted a number of signaling pathways that are important in TAM phenotype and function. Nuclear factor-kappaB (NF-kappaB) is considered the master regulator of inflammatory and immune responses. Recently several genetic studies have indicated NF-kappaB is an important pathway in TAM for the integration of signals from the tumor microenvironment that promote carcinogenesis. This review will focus on the role of NF-kappaB in TAM and the potential of targeting this pathway as a novel therapeutic strategy against cancer.