tbuckley/cabot-search huggingface dataset:
Pathobiology of pulmonary arterial hypertension
Authors: S. Eddahibi, N. Morrell, M-P. d'Ortho, R. Naeije, S. Adnot
Journal: European Respiratory Journal (2002)

Recent years have witnessed important advances in the understanding of the pathophysiology of primary pulmonary hypertension (PPH). Both genetic and mechanistic studies have succeeded in identifying new molecular pathways relevant to the process of pulmonary vascular remodelling, which underlies PPH. Mutations in the type II bone morphogenetic protein (BMP) receptor (BMPR)-II are now considered to be the genetic basis for familial PPH and ∼30% of cases of sporadic PPH. The identification of the relevance of the BMP pathway to the aetiology of PPH now raises many questions about the link between the BMPR-II mutant genotype and the PPH phenotype. As PPH does not develop in all subjects with BMPR-II mutations, environmental or associated genetic factors may play a crucial role. Among these, the finding of an association between PPH and the L-allelic variant of the serotonin transporter (5-HTT) gene indicates that 5-HTT, which controls smooth muscle hyperplasia, probably contributes to susceptibility to PPH or is an important modifier of the PPH phenotype. Recognition of these molecular pathways should provide insight into the pathogenesis not only of primary pulmonary hypertension, but also of secondary forms of pulmonary hypertension. This should soon lead to the development of new and more selective therapeutic approaches to pulmonary hypertension.
The treatment of AIDS-related lymphoma. French-Italian Cooperative Study Group
Authors: U. Tirelli
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Levine et al<sup>1</sup>have recently reported in<i>JAMA</i>that low-dose chemotherapy with central nervous system (CNS) prophylaxis and zidovudine maintenance did not compromise the therapeutic outcome of 42 patients with non-Hodgkin's lymphoma (NHL) related to the acquired immunodeficiency syndrome (AIDS). However, patients with poor prognosis, ie, those with low performance status and presence of opportunistic infections (OIs), were not eligible for entry into this study. We in the French-Italian Cooperative Study Group have recently performed a prospective study in patients with poor-prognosis AIDS-related NHL, defined as those with performance status greater than 3 and/or presence of OIs. We used a low-dose chemotherapeutic regimen with CNS prophylaxis in combination with antiretroviral therapy, the aim being to reduce both the toxic effects on the bone marrow and the occurrence of OIs. The chemotherapeutic regimen employed was that used by the European Organization on Research and Treatment of
Genomic Background Drives the Divergence of Duplicated Amylase Genes at Synonymous Sites in Drosophila
Authors: Z. Zhang
Journal: Molecular Biology and Evolution (2003)

In some Drosophila species, there are two types of greatly diverged amylase (Amy) genes (Amy clusters 1 and 2), each encoding active amylase isozymes. Cluster 1 is located at the middle of its chromosomal arm, and the region has a normal local recombination rate. However, cluster 2 is near the centromere, and this region is known to have a reduced recombination rate. Although nonsynonymous substitutions follow a molecular clock, synonymous substitutions were accelerated in cluster 2 after gene duplications. This resulted in a higher GC content at the third codon position (GC3) and codon usage bias in cluster 1, and lower GC3 content and codon usage bias in the cluster 2. However, no systematic difference in GC content was observed in the first and second codon positions or the 3′-flanking regions. Therefore, differences in local recombination rate rather than mutation bias might explain the divergence at synonymous sites between the two Amy clusters within species (Hill-Robertson effect). Alternatively, the different patterns and levels of expression between the two clusters may imply that the reduced expression level in cluster 2 caused by chromatin potentiation decreased the codon bias. Both of these hypotheses imply the importance of the genomic background as a driving force of divergence between non-tandemly duplicated genes.
Abstract 215: CSE1L as a potential target to sensitize ovarian cancer cells to cisplatin
Authors: Annalisa Lorenzato, Martina Olivero, Cosimo Martino, Nadia Dani, Daniele Musiani, Raffaele Calogero, Maria Flavia Di Renzo
Journal: Cancer Research (2010)

Abstract Human ovarian cancer is frequently (70% of cases) at advanced stage at presentation and requires multimodality treatment, consisting of cytoreductive surgery and chemotherapy based on platinum-drugs and taxanes. Patients are initially responsive to this treatment, but, in most cases, experience disease relapse because tumour cells acquire drug resistance. We demonstrated that the Hepatocyte Growth Factor (HGF) sensitizes to cisplatin (CDDP) and taxol an ovarian carcinoma cell line known to be resistant to platinum drugs: SK-OV-3, leading to an increased cancer cell death at very low drug doses both in vitro and in an animal model (Bardella et al., 2007; Rasola et al., 2004). This was an unexpected finding as HGF and its tyrosine kinase receptor, encoded by the MET oncogene, drives cell proliferation, survival and invasiveness during development and tumorigenesis. We also demonstrated that this effect is mediated by p38MAPK, which overwhelms the concomitant HGF activation of survival pathways, as the expression of a dominant negative form of p38MAPK abrogates the sensitization effect of HGF (Coltella et al., 2006). Using oligonucleotide microarrays, we studied the transcriptional responses of cell treated with CDDP in the presence or in the absence of HGF, and found that HGF pre-treatment modifies the transcriptional response to CDDP not only in SK-OV-3, but also in NIH-OVCAR-3, and TOV-21G ovarian cancer cells. The up- or down-modulation of the most differentially expressed genes found in common within these cell lines was reverted when the cells expressed a dominant negative form of p38MAPK, upholding once again the involvement of p38MAPK in this phenomenon. Among the top-ranked differentially expressed genes, which we identified, we focused functional studies on CSE1L/CAS. This gene is a nuclear transporter involved in both proliferation and apoptosis found to be amplified and over-expressed in ovarian cancer. Knocking down of CSE1L/CAS made ovarian cancer cells sensitized to low doses of cisplatin and triggered apoptosis while had no effect on other cancer and normal cell lines. In conclusion, we show that HGF and CDDP modulate transcription in ovarian cancer cells and that this transcriptional response is involved in apoptosis regulation. We also provide the proof-of-concept that the identified genes might be targeted to either increase the efficacy of chemotherapeutics or to revert chemotherapy resistance. 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 215.
Circadian and Melatonin Disruption by Exposure to Light at Night Drives Intrinsic Resistance to Tamoxifen Therapy in Breast Cancer
Authors: Robert T. Dauchy, Shulin Xiang, Lulu Mao, Samantha Brimer, Melissa A. Wren, Lin Yuan, Muralidharan Anbalagan, Adam Hauch, Tripp Frasch, Brian G. Rowan, David E. Blask, Steven M. Hill
Journal: Cancer Research (2014)

Resistance to endocrine therapy is a major impediment to successful treatment of breast cancer. Preclinical and clinical evidence links resistance to antiestrogen drugs in breast cancer cells with the overexpression and/or activation of various pro-oncogenic tyrosine kinases. Disruption of circadian rhythms by night shift work or disturbed sleep-wake cycles may lead to an increased risk of breast cancer and other diseases. Moreover, light exposure at night (LEN) suppresses the nocturnal production of melatonin that inhibits breast cancer growth. In this study, we used a rat model of estrogen receptor (ERα(+)) MCF-7 tumor xenografts to demonstrate how altering light/dark cycles with dim LEN (dLEN) speed the development of breast tumors, increasing their metabolism and growth and conferring an intrinsic resistance to tamoxifen therapy. These characteristics were not observed in animals in which the circadian melatonin rhythm was not disrupted, or in animals subjected to dLEN if they received nocturnal melatonin replacement. Strikingly, our results also showed that melatonin acted both as a tumor metabolic inhibitor and a circadian-regulated kinase inhibitor to reestablish the sensitivity of breast tumors to tamoxifen and tumor regression. Together, our findings show how dLEN-mediated disturbances in nocturnal melatonin production can render tumors insensitive to tamoxifen.
Family Outbreak of Severe Pneumonia Induced by H7N9 Infection
Authors: Zhijun Jie, Juan Xie, Zebao He, Yuanlin Song, Yunwen Hu, Fangming Li, Ying Shen, Jindong Shi, Yanchao He, Qihui Huang, Yong Gu, Chunxue Bai
Journal: American Journal of Respiratory and Critical Care Medicine (2013)
Increased levels of antibodies to cytokeratin 18 in patients with rheumatoid arthritis and ischaemic heart disease
Authors: D L Mattey, P T Dawes, N B Nixon, L Goh, M J Banks, G D Kitas
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To determine whether raised levels of antibodies to CK18 in patients with RA are associated with ischaemic heart disease (IHD). <b>Methods:</b> IgA, IgG, and IgM antibodies to CK18 were measured by enzyme linked immunosorbent assay (ELISA) in patients with RA with (n = 34) or without (n = 28) IHD. The relationship between CK18 antibody levels and markers of inflammatory and/or cardiovascular disease was examined. <b>Results:</b> Initial analysis showed that IgG antibody levels to CK18 were higher in patients with RA with IHD than in those without (50.1 <i>v</i> 34.5 AU, p = 0.047), although significance was lost after correction for multiple comparisons. Further analysis showed a significant difference (p = 0.015) between patients with IHD and a positive family history, and patients without IHD and a negative family history (53.7 <i>v</i> 29.0 AU, Kruskal-Wallis multiple comparison Z value test). There was also a significant trend of increasing 10 year cardiovascular risk with increasing CK18 IgG antibody levels (p = 0.01). No association was found between CK18 antibody levels and conventional markers of inflammation or cardiovascular disease, but an association was found between levels of CK18 IgG and IgG antibodies to cytomegalovirus (CMV) (Spearman's <i>r</i><sub>s</sub> = 0.379, p<sub>corr</sub> = 0.04). No evidence for cross reactivity of CK18 antibodies with CMV antigens was found. <b>Conclusion:</b> Levels of IgG antibodies to CK18 are raised in patients with RA with IHD, particularly if they also have a positive family history. This may reflect damage to CK18 containing cells in the cardiac vasculature and/or in atherosclerotic plaques, and may be a useful additional marker for the identification of patients with, or likely to develop, IHD.
Radionuclide Demonstration of Relative Increased Blood Flow in Uniappendicular Secondary Hypertrophic Osteoarthropathy
Authors: LEONARD ROSENTHALL, DAVID HAWKINS, SYLVESTER CHUANG
Journal: Clinical Nuclear Medicine (1978)

A rare case of hypertrophic osteoarthropathy (HO) limited to one lower extremity is described in a male with a history of familial polyposis coli and bilateral aortofemoral grafts. The precise etiology remains unknown. Radiography depicted the HO, but 99m Tc-methylene diphosphonate imaging showed more extensive involvement. An intra-aortic injection of 99m Tc-macroaggregates of albumin portrayed a larger blood flow to the involved limb compared to the contralateral extremity. The major part of this increase was in bone rather than in the adjacent soft tissue.
THE SUPRAVITAL STAINING OF VACCINE BODIES
Authors: Edmund V. Cowdry
Journal: The Journal of Experimental Medicine (1922)

Vaccine bodies in living corneal cells may be specifically stained by the addition of a small quantity of brilliant cresyl blue 2 B to the physiological salt solution in which they are being observed. Their appearance by this method (Figs. 3 to 17) corresponds with that seen in fixed preparations (Figs. 22 to 42). Both lines of study reveal the existence of traces of similar material in unvaccinated corneal cells. As this increases in amount during the reaction, it behaves like an integral, cytoplasmic constituent of fluid consistency and shows no evidence of being endowed with any measure of independent vitality. The low grade of structural differentiation which it does exhibit, in living cells as well as in fixed tissues, is not suggestive of the presence within it of independent microorganisms. The material differs radically in its morphology and microchemical reactions from the granules observed by MacCallum and Oppenheimer in vaccine lymph.
Huntingtin cleavage product A forms in neurons and is reduced by gamma-secretase inhibitors
Authors: Kimberly B Kegel, Ellen Sapp, Jonathan Alexander, Patrick Reeves, Dorothee Bleckmann, Linsday Sobin, Nicholas Masso, Antonio Valencia, Hyunkyung Jeong, Dimitri Krainc, James Palacino, Daniel Curtis, Rainer Kuhn, Claudia Betschart, Miguel Sena-Esteves, Neil Aronin, Paolo Paganetti, Marian DiFiglia
Journal: Molecular Neurodegeneration (2010)

The mutation in Huntington's disease is a polyglutamine expansion near the N-terminus of huntingtin. Huntingtin expressed in immortalized neurons is cleaved near the N-terminus to form N-terminal polypeptides known as cleavage products A and B (cpA and cpB). CpA and cpB with polyglutamine expansion form inclusions in the nucleus and cytoplasm, respectively. The formation of cpA and cpB in primary neurons has not been established and the proteases involved in the formation of these fragments are unknown. Delivery of htt cDNA into the mouse striatum using adeno-associated virus or into primary cortical neurons using lentivirus generated cpA and cpB, indicating that neurons in brain and in vitro can form these fragments. A screen of small molecule protease inhibitors introduced to clonal striatal X57 cells and HeLa cells identified compounds that reduced levels of cpA and are inhibitors of the aspartyl proteases cathepsin D and cathepsin E. The most effective compound, P1-N031, is a transition state mimetic for aspartyl proteases. By western blot analysis, cathepsin D was easily detected in clonal striatal X57 cells, mouse brain and primary neurons, whereas cathepsin E was only detectible in clonal striatal X57 cells. In primary neurons, levels of cleavage product A were not changed by the same compounds that were effective in clonal striatal cells or by mRNA silencing to partially reduce levels of cathepsin D. Instead, treating primary neurons with compounds that are known to inhibit gamma secretase activity either indirectly (Imatinib mesylate, Gleevec) or selectively (LY-411,575 or DAPT) reduced levels of cpA. LY-411,575 or DAPT also increased survival of primary neurons expressing endogenous full-length mutant huntingtin. We show that cpA and cpB are produced from a larger huntingtin fragment in vivo in mouse brain and in primary neuron cultures. The aspartyl protease involved in forming cpA has cathepsin-D like properties in immortalized neurons and gamma secretase-like properties in primary neurons, suggesting that cell type may be a critical factor that specifies the aspartyl protease responsible for cpA. Since gamma secretase inhibitors were also protective in primary neurons, further study of the role of gamma-secretase activity in HD neurons is justified.
Emergency coronary artery revascularization of patients with acute myocardial infarction: you can ... but should you?
Authors: H D McIntosh, R A Buccino
Journal: Circulation (1979)

CORONARY ARTERY DISEASE is a life- threatening illness with an unpredictable clinical course.The intensity and quality of pain and the in- cidence of sudden and unexpected death creates fear in both the patient and those, including the physician, responsible for the care.The astute physician realizes that allaying the fear of the patient and his family is as important as the relief of pain.In planning therapy, however, the physician must separate his own fears and uncertainties from those of the patient and the patient's family.
VENOGRAPHIC DIAGNOSIS OF THROMBOPHLEBITIS OF THE LOWER EXTREMITIES
Authors: H. I. Biegeleisen
Journal: JAMA (1942)

<h3>To the Editor:—</h3> In the April 4 issue ofThe Journalappeared an article entitled "The Venographic Diagnosis of Thrombophlebitis of the Lower Extremities" by Dr. Arnold Starr and his associates. The authors describe a method of visualizing the deep venous system of the lower extremities as an aid in the diagnosis of thrombophlebitis. The technic that they use involves the injection of diodrast into a deep vein behind the external malleolus, which is found after making a small incison. This method is that of G. Bauer, who described it for the first time in the<i>Acta chirurgica Scandinavica</i>, published in 1940. The studies made by Starr and his associates are interesting and significant, but I should like to call attention to a somewhat similar method of visualizing deep venous thrombosis which I published in 1939. This article entitled "Unilateral Enlargement of the Lower Extremities Accompanying Varicose Veins, with Roentgen
Yoga-Based Intervention for Carpal Tunnel Syndrome
Authors: Marian S. Garfinkel, Atul Singhal, Warren A. Katz, David A. Allan, Rosemary Reshetar, H. Ralph Schumacher, Jr
Journal: JAMA (1998)

Context.—Carpal tunnel syndrome is a common complication of repetitive activities and causes significant morbidity.Objective.—To determine the effectiveness of a yoga-based regimen for relieving symptoms of carpal tunnel syndrome.Design.—Randomized, single-blind, controlled trial.Setting.—A geriatric center and an industrial site in 1994-1995.Patients.—Forty-two employed or retired individuals with carpal tunnel syndrome (median age, 52 years; range, 24-77 years).Intervention.—Subjects assigned to the yoga group received a yoga-based intervention consisting of 11 yoga postures designed for strengthening, stretching, and balancing each joint in the upper body along with relaxation given twice weekly for 8 weeks. Patients in the control group were offered a wrist splint to supplement their current treatment.Main Outcome Measures.—Changes from baseline to 8 weeks in grip strength, pain intensity, sleep disturbance, Phalen sign, and Tinel sign, and in median nerve motor and sensory conduction time.Results.—Subjects in the yoga groups had significant improvement in grip strength (increased from 162 to 187 mm Hg; P =.009) and pain reduction (decreased from 5.0 to 2.9 mm; P =.02), but changes in grip strength and pain were not significant for control subjects. The yoga group had significantly more improvement in Phalen sign (12 improved vs 2 in control group; P =.008), but no significant differences were found in sleep disturbance, Tinel sign, and median nerve motor and sensory conduction time.Conclusion.—In this preliminary study, a yoga-based regimen was more effective than wrist splinting or no treatment in relieving some symptoms and signs of carpal tunnel syndrome.
Prevalence of asthma with aspirin hypersensitivity in the adult population of Poland
Authors: L. Kasper, K. Sladek, M. Duplaga, G. Bochenek, J. Liebhart, U. Gladysz, J. Malolepszy, A. Szczeklik
Journal: Allergy (2003)

Background: Acetylsalicylic acid (ASA) and other nonsteroid anti‐inflammatory drugs (NSAIDs) are reported to account for 21–25% of all adverse drug reactions. Some asthmatics may react to ASA and other NSAIDs with acute bronchoconstriction, profuse rhinorrhea and skin flushing. This is a distinct clinical syndrome called aspirin‐induced asthma (AIA). The prevalence of AIA among asthmatic patients in Poland has not been previously assessed. Methods: A questionnaire survey of 12 970 adults of both sexes, randomly selected from the population of Poland. Results: The prevalence of AIA in the general population of Poland was estimated as 0.6%. Thirty patients (4.3%; 95% CI: 2.8–5.8) of 703 asthmatics (5.4% of general population) reported symptoms attesting to hypersensitivity to aspirin. In 27% of them the reactions were precipitated by aspirin, whereas in the remaining subjects by other NSAIDs. Conclusions: The prevalence of AIA in Poland is 4.3%, being somewhat lower than in Finland and Australia, where it was recently reported to account for 8.8 and 10.9% of the adult asthmatics, respectively. These figures indicate that aspirin hypersensitivity might be a significant community problem.
Yellow nail syndrome in rheumatoid arthritis: report of three cases.
Authors: P C Mattingly, D H Bossingham
Journal: Annals of the Rheumatic Diseases (1979)

We report the occurrence of the yellow nail syndrome in 3 patients with rheumatoid arthritis. In 2 patients the development of the syndrome was related to severe chest infections, and there was evidence of immunodeficiency, consisting in 1 case of a persistently low serum IgA level and in the other of a generalised marrow suppression. The third patient gave a history of recurrent sinusitis and showed evidence of previous chest infections and pulmonary fibrosis, but has no gross evidence of immunodeficiency. We have found only 1 previous brief mention of a patient with the yellow nail syndrome and rheumatoid arthritis.
Value of DNA image cytometry in the prediction of malignant change in Barrett's oesophagus.
Authors: P D James, M Atkinson
Journal: Gut (1989)

DNA image cytometry was performed on Feulgen stained sections from 91 biopsies obtained during prospective endoscopic surveillance of 55 patients with Barrett's oesophagus. Aneuploid cells were detected in specimens from six of these patients. Four subsequently developed dysplasia and adenocarcinoma but, in the other two, biopsies had been reported as showing specialised epithelium only, with no apparent dysplasia and no evidence of malignancy on clinical follow up to date. In two of the four patients who subsequently developed carcinoma, aneuploid cells were only found in biopsies showing overt dysplasia or carcinoma but in the two other patients aneuploid cells were present in biopsies taken early in the clinical course before any dysplasia had been identified on the original reports. The presence of aneuploid cells on cytometry of these 'benign' biopsies allowed us, on histological review, to identify areas of atypia which were interpreted as mild dysplasia. In this series aneuploidy was always associated with some morphological abnormality varying from mild dysplasia to frank carcinoma. Aneuploid cells were not shown in material from one patient who had an oesophagectomy for dysplasia or in biopsy material from four patients showing 'indefinite dysplasia'. DNA cytometry combines an objective assessment of epithelial atypia with the advantage of detecting rare cellular aneuploidy and the ability to correlate these events with morphology. It should assist in the more accurate diagnosis of dysplasia and prove useful in identifying those patients with Barrett's oesophagus who are at greater risk of subsequently developing malignancy.
Chemomodulation of sequential high-dose cytarabine by fludarabine in relapsed or refractory acute myeloid leukemia: a randomized trial of the AMLCG
Authors: M Fiegl, M Unterhalt, W Kern, J Braess, K Spiekermann, P Staib, A Grüneisen, B Wörmann, D Schöndube, H Serve, A Reichle, M Hentrich, X Schiel, C Sauerland, A Heinecke, C Rieger, D Beelen, W E Berdel, T Büchner, W Hiddemann
Journal: Leukemia (2013)
CD44-ligation induces, through ERK1/2 pathway, synthesis of cytokines TNF-α and IL-6 required for differentiation of THP-1 monoblastic leukemia cells
Authors: S Bourcier, A Sansonetti, L Durand, C Chomienne, J Robert-Lézénés, F Smadja-Joffe
Journal: Leukemia (2010)