tbuckley/cabot-search huggingface dataset:
S143 Evidence that Type I interferon drives pulmonary arterial hypertension
Authors: PM George, E Oliver, BE Schreiber, AM Holmes, M Southwood, SJ Wort, N Bartlett, P Dorfmuller, NW Morrell, G Coghlan, M Humbert, L Zhao, JA Mitchell
Journal: Thorax (2013)

<h3>Rationale</h3> There is increasing evidence of a link between interferon (IFN) and pulmonary arterial hypertension (PAH). Conditions such as HIV and Systemic sclerosis (SSc) where endogenous IFN levels are chronically elevated are strongly associated with PAH. Furthermore, therapeutic use of type I IFN is now known to cause PAH and increase the systemic release of endothelin (ET)-1 in some patients. The link between IFN therapy and PAH was formally recognised at the 5-yearly World Symposium on Pulmonary Hypertension (Nice, Feb 2013). Our group has identified the mitogen ET-1 and the archetypal interferon stimulated gene - interferon gamma inducible protein 10 (IP10) as candidate mediators for IFN induced PAH. Using a comprehensive approach incorporating human pulmonary vascular cells <i><i>in vitro</i></i>, genetically modified mice <i><i>in vivo</i></i> and clinical samples with patient data we sought to explore the role of type I IFN in PAH. <h3>Methods</h3> Primary cells were cultured and responses measured using standard approaches. Serum cytokine and ET-1 levels were measured by ELISA. The role of type I IFN in PAH <i><i>in vivo</i></i> was determined using type I IFN receptor knock out (IFNAR1 <sup>-/-</sup>) mice and the chronic hypoxia model of PAH. <h3>Results</h3> Human pulmonary artery smooth muscle cells expressed the type I IFN receptor and released ET-1 (Fig. 1a) and IP10 in response to IFNα. In patients with SSc associated PAH, serum IP10 and ET-1 levels were raised and correlated positively together (Fig. 1b). In addition IP10 correlated strongly with pulmonary haemodynamics and 6 minute walk distance (Fig. 1b). Finally, IFN was found to mediate PAH <i><i>in vivo</i></i> since mice lacking a functioning type I IFN receptor were protected from hypoxia induced PAH (Fig. 1c). <h3>Discussion and Conclusions</h3> These novel data reveal a clear pathological role for type I IFN in PAH and provide crucial insight into the mechanisms underpinning pulmonary vascular toxicity associated with type I IFN therapies. Furthermore, endogenous IFN elevated in autoimmune disease or viral infection, are now implicated in PAH. We conclude that type I IFN, via an action of IFNAR1 and potentially through ET-1 and IP10, mediates PAH and may represent a novel therapeutic target.
The Natural History of Recurrent Bacteriuria in Schoolgirls
Authors: Calvin M. Kunin
Journal: New England Journal of Medicine (1970)

A long-term study of recurrent bacteriuria was carried out in girls in whom urinary-tract infection was detected during school surveys. In most of them management was limited to short-term, specific chemotherapy coupled with frequent follow-up examinations. Eighty per cent of recurrences were due to reinfection with a new organism. Each course of therapy extracted 20 to 25 per cent of white and about 40 per cent of Negro girls into long-term remission. Recurrences in the population closely followed a logarithmic decay curve, which demonstrated the marked effect of age and race. Socioeconomic status and vesicoureteral reflux had no significant effect on recurrence rates. Recurrences tended to be less frequent the longer the girls remained free of infection, but they were still at higher risk of acquiring bacteriuria than the general population. Marriage and pregnancy were times of increased risk.
Identification of Der p 23, a Peritrophin-Like Protein, As a New Major Dermatophagoides Pteronyssinus Allergen Associated with the Peritrophic Matrix of Mite Fecal Pellets
Authors: Susanne Vrtala, Margit Weghofer, Anne Casset, Kuan-Wei Chen, Monika Grote, Michael Kneidinger, Yvonne Resch, Wayne Thomas, Enrique Fernandez-Caldas, Adriano Mari, Ashok Purohit, Gabrielle Pauli, Friedrich Horak, Walter Keller, Peter Valent, Rudolf Valenta
Journal: Journal of Allergy and Clinical Immunology (2013)
Antihypertensive Effect of the Oral Angiotensin Converting-Enzyme Inhibitor SQ 14225 in Man
Authors: Haralambos Gavras, Hans R. Brunner, Gustave A. Turini, Glenn R. Kershaw, Charles P. Tifft, Sergio Cuttelod, Irene Gavras, Robert A. Vukovich, Doris N. McKinstry
Journal: New England Journal of Medicine (1978)

We investigated the antihypertensive effect of the angiotensin converting-enzyme inhibitor SQ 14225 in 12 hypertensive patients for periods of three to 24 weeks. Blood pressure decreased in all patients (from 177 +/- 8/110 +/- 2 to 136 +/- 6/88 +/- 2 mm Hg--mean +/- S.E.); oral doses ranged from 400 to 1000 mg daily. Concomitant effects noted were small increases in plasma potassium concentration and pulse rate. One patient experienced a transient febrile reaction. Plasma renin activity rose during treatment, plasma aldosterone decreased, and angiotensin-converting-enzyme activity was virtually eliminated. There was no significant correlation between pretreatment plasma renin activity and degree of blood-pressure fall with SQ 14225. The exact mechanisms contributing to the blood-pressure-lowering effect of this agent remain unclear. SQ 14225 is a promising new antihypertensive agent, effective in patients refractory to traditional medical therapy.
1011 DIFFERENCE OF STAGE, TREATMENT STRATEGY AND SURVIVAL OF HEPATOCELLULAR CARCINOMA PATIENTS BETWEEN PAST AND RECENT PERIODS: ANALYSIS OF 7852 CASES FROM 1986 TO 2010
Authors: K.-M. Kee, S.-N. Lu, J.-H. Wang, C.-C. Wang, T.-Y. Chen, Y.-J. Huang
Journal: Journal of Hepatology (2012)
P18.01 * COMPLEMENTARY THERAPY USE IN A COHORT OF SWISS GLIOMA PATIENTS
Authors: G. Eisele, U. Roelcke, K. Conen, F. Huber, T. Weiss, S. Hofer, O. Heese, M. Westphal, M. Weller
Journal: Neuro-Oncology (2014)

Within a short time from diagnosis glioma patients usually become aware that the tumor is incurable and that conventional therapies have only limited success. Therefore it is not uncommon that these patients seek second opinions or contact patient self-help groups. Moreover, it is common that patients seek for other treatments themselves, as an adjunct or alternative to conventional therapies. We here describe complementary therapy (CT) use in a cohort of glioma patients treated at three neuro-oncology centers in Switzerland. A previously developed questionnaire from the German Glioma Network was adapted for Swiss conditions and distributed consecutively in the outpatient clinics. We retrieved questionnaires from 139 patients with gliomas of WHO grades II to IV. Fifty-one percent of the participants reported the use of CT. The main motivation for the use of CT was to actively participate in the fight against the disease. However, only a minority of patients using CT was counselled and accompanied by a physician for this treatment. Regarding reimbursement, health insurances in Switzerland are obliged to cover the costs of some defined CT. However, reimbursement was crucial for only 30 percent of the patients in the decision for CT use. CT usage in glioma patients is more frequent in this Swiss cohort (51 %) compared to a cohort from the German Glioma Network (40 %) and probably heavily underestimated in general. Patients often use sources for information and therapeutics outside neuro-oncology centers and outside medical competence. Physicians involved in the treatment of glioma patients should be aware of self-treatments in addition to standard of care.
AB0351 1,25-dihydroxyvitamin d3 inhibits the rankl pathway and impacts on the production of pathway-associated cytokines in early rheumatoid arthritis
Authors: J. Luo, X. Li
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) was a common chronic autoimmune disorder characterized with synovial inflammation. Bone loss in the inflamed joints occurred in the early stage of the disease, followed by the destruction of articular cartilage and bones. During the processing of the disease, the signaling pathway of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) was crucial in osteoclasts differentiation and activation. <h3>Objectives</h3> To study effects of 1,25-dihydroxyvitamin D3 (1,25(OH)<sub>2</sub>D<sub>3</sub>) on RANKL signaling pathway and pathway-associated cytokines in patients with rheumatoid arthritis (RA). <h3>Methods</h3> Receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), IFN-γ, IL-6, TNF-α, IL-17 and IL-4 were examined in 54 patients with active RA using a cytometric bead array (CBA) and an enzyme-linked immunosorbent assay (ELISA). <h3>Results</h3> After 72 hours of incubation of peripheral blood mononuclear Cell (PBMC) with 1,25(OH)<sub>2</sub>D<sub>3</sub>, the levels of RNAKL, TNF-α, IL-17 and IL-6 significantly decreased. 1,25(OH)<sub>2</sub>D<sub>3</sub> had no significantly impact on the level of OPG, RANKL/OPG and IL-4. The ratios of IL-17/IL-4, TNF-α/IL-4, IFN-γ/IL-4 significantly decreased in 1,25(OH)<sub>2</sub>D<sub>3</sub> testing groups. <h3>Conclusions</h3> The present study demonstrated that 1,25(OH)<sub>2</sub>D<sub>3</sub> reduces the production of RANKLE and the secretion of TNF-α, IL-17, and IL-6 in PBMC of RA patients, which indicates that 1,25(OH)<sub>2</sub>D<sub>3</sub> might be able to decrease damage of cartilage and bone in RA patients by regulating the expression of RANKL signaling pathway and pathway-associated cytokines. <h3>References</h3> <b>Disclosure of Interest</b>: None Declared
Allergic Manifestations after the Injection Treatment of Varicose Veins
Authors: Eliza A. Melkon, Dorothy K. Scheidell
Journal: New England Journal of Medicine (1947)

THE treatment of varicose veins by the injection method started in Europe, being used in 1904 by Tavel and in 1912 by Linser. During and after World War I numerous sclerosing agents were employed by Sicard and Gaugier, Montpellier, Genevrier and Dowthwaite, Noul and Troisier. Melkon1 reviewed the history of the treatment of varicose veins in a paper published in 1929. Since then, various sclerosing agents have been used by many surgeons who gave injections freely and without too much consideration of possible dangers. It is time to call attention to the possible dangers in the use of sclerosing material. . . .
AB0288 Anti citrulline and homocitrulline antibodies are synergistic diagnostic parameters in RA
Authors: H. Bang, K. Egerer, B. Lehmann, A. Krämer, E. Feist, G.R. Burmester
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Current perception of RA pathogenesis suggests that posttranslational modification (PTM) of either arginine (into citrulline) or lysine (into homocitrulline) residues in antigens are crucial for the generation of specific autoantibodies in RA. <h3>Objectives</h3> To examine how anti–citrullinated protein antibody (ACPA) and anti-homocitrulline protein antibody (AHPA) arise in the immune response of clinically overt rheumatoid arthritis (RA), and to analyze the influence of B cell directed therapy on antibody reactivity. <h3>Methods</h3> Homocitrullin residues were inserted into human mutated vimentin by non-enzymatic carbamoylation, in contrast to the enzymatic citrullination. Peptide librariesfrom the identified major RA epitope of mutated vimentin weregenerated with citrulline and homocitrulline residues, respectively. Reactivity to 5 distinct modified peptides was measured by enzymelinked immunosorbent assay and validatedwith sera from human healthy individuals and disease controls (systemic autoimmune diseases such as SLE and Sjögren's syndrome). The study included 142 patients (mean age at inclusion 54.3±12.6 years) with RA (fulfilled the ACR 1987 RA criteria), who started on treatment with TNF-inhibitor followed by B-cell directed therapy. Multiple consecutive serum samples from RA patients were included for analysis of antibody titers in the follow-up. <h3>Results</h3> Sensitivities of 86,8% and 69,2% were calculated for the ACPA and AHPA assays, respectively. Sera from healthy persons and disease control groups showed a comparable specificity for both assays (ACPA 97% and AHPA 91%) and none had anti-antibodies against the unmodifed vimentin. With peptide assay distinctive only in citrulline and homocitrulline, more than 45% of RA patients were analyzed to have both ACPA and AHPA, and singular AHPA response was not observed. The lowest concentration of ACPA and AHPA were estimated to be 60 μg/ml and 25 μg/ml, respectively. Remarkably, after one cycle of RTX treatment a bisection of AHPA levels and a 25% reduction of ACPA levels were observed. Patients under TNF blockers without DAS28 remission after a period of 6 months showed a lesser reduction of ACPA and AHPA levels of only 15 – 28%. <h3>Conclusions</h3> Our findings indicate that the significant serological variation in RA patients may be an indication that RA may encompass a number of distinct serologic entities, of which particularly ACPA and AHPA may play a role in different phases of RA pathogenesis. <h3>Disclosure of Interest</h3> H. Bang Employee of: Orgentec Diagnostika GmbH, K. Egerer: None Declared, B. Lehmann: None Declared, A. Krämer Employee of: Orgentec Diagnostika GmbH, E. Feist: None Declared, G. R. Burmester: None Declared
Abstract 1291: The neurotransmitter dopamine normalizes tumor neo-vessels by modulating G protein coupled receptor signaling in the cells of tumor microenvironment
Authors: Debanjan Chakroborty, Chandrani Sarkar, Hongmei Yu, Shubham Bakshi, Partha Sarathi Dasgupta, Sujit Basu
Journal: Cancer Research (2010)

Abstract Tumor neo-vessels, unlike the normal are disorganized, tortuous and leaky. Such dysfunctional blood vessels within the tumors pose significant obstacle for the proper delivery of anticancer drugs into the tumor tissues and response to radiation. Thus normalization of these tumor neo-vessels by different approaches has shown to improve the therapeutic efficacies of conventional anti-neoplastic drugs and radiation therapy. We here show for the first time that the neurotransmitter dopamine normalizes tumor blood vessels in mice bearing orthotopic human prostate cancer by manipulating the cellular components of the tumor microenvironment through G protein coupled receptor signaling. This result is significant because dopamine or dopamine like drugs can be utilized synergistically with either anti-cancer drugs or radiation for the treatment of cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1291.
Abstract 4055: Real-time quantitation of primary transcripts of microRNA genes
Authors: Yu Liang, Fangqi Hu, Emanuel Langit, Julia Lu, Pius Brzoska, Caifu Chen
Journal: Cancer Research (2010)

Abstract Regulation of mature microRNA (miRNA) expression has been shown during the course of biogenesis under different contexts: from transcription, processing of pri-miRNA to pre-miRNA by Drosha, to processing of pre-miRNA to mature miRNA by Dicer. A mature miRNA can be processed from two or more stem-loop precursor loci, which are denoted with numeric suffixes such as −1, −2, etc. As of the 14th Release of the miRBase, there are 154 genes among the 750 miRNA genes that belong to this category. To interrogate regulation of miRNA expression at the transcriptional level for those that can be processed from multiple genomic locations, it requires assays to specifically quantitate the precise locus of interest. We have developed a pipeline to design and select real-time RT-PCR assays to quantitate primary transcripts of miRNA genes. These assays are designed against genomic DNA sequence so the genomic DNA needs to be removed by prior enzyme treatment. We showed that the TaqMan® Pri-miRNA Assays have minimally detectable or no background using either cell lysates or commercial tissue total RNA. Excellent linearity was seen using cDNA synthesized from total RNA, or using 1ng/ul or greater of genomic DNA. The specificity of the assays to distinguish loci that are processed into identical mature miRNA was demonstrated using subcloned plasmids, as well as using breast cancer cell lines that showed concordant expression patterns among such loci with published data in human breast cancer. The TaqMan® Pri-miRNA Assays will be a useful tool to identify the precise loci that contribute to the mature miRNA expression of interest at the transcription level, so as to further investigate the regulatory mechanisms for the differential expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4055.
Transfer of Allergen-Specific IgE-Mediated Hypersensitivity with Allogeneic Bone Marrow Transplantation
Authors: Jan M. Agosti, Jay D. Sprenger, Lawrence G. Lum, Robert P. Witherspoon, Lloyd D. Fisher, Rainer Storb, William R. Henderson
Journal: New England Journal of Medicine (1988)

We investigated whether allergen-specific IgE-mediated hypersensitivity is transferred by bone marrow transplantation. Twelve patients, 14 to 47 years of age, undergoing allogeneic bone marrow transplantation for the treatment of hematologic cancer were selected, along with their donors, by a screening questionnaire for a history of atopy in the donor. We evaluated these donor-recipient pairs before transplantation and at several points afterward for immediate skin-test reactivity to 17 allergens. For allergens for which pretransplantation skin tests had been positive in the donors and negative in the recipients, 20 of 46 post-transplantation skin tests were positive in 8 of the 11 recipients who survived for more than one year after transplantation. For allergens for which both donors and recipients had had negative skin tests before transplantation, only 6 of 256 tests (2.3 percent) were positive in the recipients after transplantation. Long-term transfer of donor-derived mite-specific IgE was demonstrated by radioallergosorbent testing in two recipients. Seven recipients either acquired or had an exacerbation of allergic rhinitis, and two recipients without a history of asthma had asthma one year after transplantation. We conclude that allergen-specific IgE-mediated hypersensitivity is adoptively transferred by bone marrow transplantation from donor to recipient by B cells with allergen-specific memory. (N Engl J Med 1988; 319:1623–8.)
Assessing the Implementation of Physician-Payment Reform
Authors: William C. Hsiao, Daniel L. Dunn, Diana K. Verrilli
Journal: New England Journal of Medicine (1993)

The Medicare program fundamentally changed its system of payment for physicians' services in 1992. Controversy over the new Medicare fee schedule has focused on three issues: the adequacy of the conversion factor used to translate resource-based relative-value units into fees; the ability of the new payment system to capture differences in work between surgeons and physicians in other specialties; and the allocation of practice expenses across services.Using a standard service in each specialty, we developed simulation methods to assess the implementation of physician-payment reform. With these methods we calculated the potential net income for each specialty, as generated by different payment scenarios, including the Medicare fee schedule.We found that Medicare's current monetary-conversion factor yields an unreasonably low level of income for most specialties. Furthermore, the Medicare fee schedule misallocates practice expenses; invasive services are reimbursed for more than actual expenses, and medical services are reimbursed for less. Thus, physicians continue to be paid more generously for invasive services. Finally, the Medicare fee schedule does recognize the wide differences in the intensity of work performed by physicians in various specialties.The misallocation of practice expenses in the Medicare fee schedule results in serious underpayment for medical services. We think it likely that physicians compensate by performing more lucrative services, such as diagnostic tests. Even if legislation is passed to deal with the misallocation of expenses, the current conversion factor still produces unreasonably low levels of payment overall, which could dissuade those considering a career in medicine from entering the field. Finally, the simulation method we developed can be used as a tool for fee negotiations.
Abstract 1874: Phosphatidylcholine synthesis as a potential therapeutic target in multiple myeloma.
Authors: Carolyne Bardeleben, Alan Lichtenstein
Journal: Cancer Research (2013)

Abstract A metabolics screen with 8226 cells treated with AICAr showed that de novo pyrimidine synthesis was inhibited. AICAr -induced apoptosis in 5 different myeloma cell lines. This screen showed a significant decrease in CDP-choline, an intermediate of the Kennedy pathway involved in de novo synthesis of phosphatidylcholine (PC). Phosphatidylcholine is the most predominant phospholipid in mammalian ER membranes. The rate limiting step in this pathway is the conversion of phosphocholine and CTP to CDP-choline via the enzyme CTP:phosphocholine cytidylyltransferase (CCT). Although it is likely that the decrease in CDP-choline is a consequence of pyrimidine starvation, the fact that this pathway showed a significant decrease within 8 hours of AICAr treatment suggested to us that this pathway may have a high flux in 8226 cells and that phosphatidylcholine synthesis may be a relevant target in myeloma cells. Multiple myeloma (MM) cells may be particularly dependent on this biosynthetic reaction because of their high consistent level of ER stress and requirement to continuously replenish ER membranes. Indeed, CCT-null mice have a defect in differentiation of B lymphocytes to plasma cells and deficiencies in Ig synthesis. To test whether this pathway remains critical in survival of malignant MM cells, we exposed MM cell lines to an inhibitor shown to inhibit CCT activity, HexPC. HexPC induced apoptosis in all MM cell lines in a concentration- and time-dependent manner. The addition of lysophosphatidylcholine (LPC), presumably converted to PC independently of the Kennedy pathway, completely rescued MM cell apoptosis. Knocking down of CCT with shRNA in myeloma cell lines also resulted in apoptosis. Apoptosis of MM cells induced by HexPC was associated with induction of ER stress as shown by enhanced phosphorylation of IRE1 and eIF-2alpha. This ER stress was also prevented when LPC was added to HexPC although LPC could not prevent similar ER stress induced by bortezomib. These results underscore the importance of this phosphatidylcholine synthesis pathway in MM cells and provide new targets for future therapy. Citation Format: Carolyne Bardeleben, Alan Lichtenstein. Phosphatidylcholine synthesis as a potential therapeutic target in multiple myeloma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1874. doi:10.1158/1538-7445.AM2013-1874