tbuckley/cabot-search huggingface dataset:
Phenotypic and functional features of human Th17 cells
Authors: Francesco Annunziato, Lorenzo Cosmi, Veronica Santarlasci, Laura Maggi, Francesco Liotta, Benedetta Mazzinghi, Eliana Parente, Lucia Filì, Simona Ferri, Francesca Frosali, Francesco Giudici, Paola Romagnani, Paola Parronchi, Francesco Tonelli, Enrico Maggi, Sergio Romagnani
Journal: The Journal of Experimental Medicine (2007)

T helper (Th) 17 cells represent a novel subset of CD4+ T cells that are protective against extracellular microbes, but are responsible for autoimmune disorders in mice. However, their properties in humans are only partially known. We demonstrate the presence of Th17 cells, some of which produce both interleukin (IL)-17 and interferon (IFN)-γ (Th17/Th1), in the gut of patients with Crohn's disease. Both Th17 and Th17/Th1 clones showed selective expression of IL-23R, CCR6, and the transcription factor RORγt, and they exhibited similar functional features, such as the ability to help B cells, low cytotoxicity, and poor susceptibility to regulation by autologous regulatory T cells. Interestingly, these subsets also expressed the Th1-transcription factor T-bet, and stimulation of these cells in the presence of IL-12 down-regulated the expression of RORγt and the production of IL-17, but induced IFN-γ. These effects were partially inhibited in presence of IL-23. Similar receptor expression and functional capabilities were observed in freshly derived IL-17–producing peripheral blood and tonsillar CD4+ T cells. The demonstration of selective markers for human Th17 cells may help us to understand their pathogenic role. Moreover, the identification of a subset of cells sharing features of both Th1 and Th17, which can arise from the modulation of Th17 cells by IL-12, may raise new issues concerning developmental and/or functional relationships between Th17 and Th1.
A phase III randomised trial comparing sequential chemotherapy using cisplatin-based regimen and paclitaxel to cisplatin-based chemotherapy alone in advanced non-small-cell lung cancer
Authors: J.P. Sculier, J.J. Lafitte, J. Lecomte, C.G. Alexopoulos, O. Van Cutsem, V. Giner, A. Efremidis, M.C. Berchier, T. Collon, A.P. Meert, A. Scherpereel, V. Ninane, M. Paesmans, T. Berghmans
Journal: Annals of Oncology (2007)
Low-Dose Chemotherapy With Central Nervous System Prophylaxis and Zidovudine Maintenance in AIDS-Related Lymphoma
Authors: Alexandra M. Levine, James C. Wernz, Lawrence Kaplan, Nat Rodman, Philip Cohen, Craig Metroka, John M. Bennett, Mark U. Rarick, Christine Walsh, James Kahn, Steven Miles, W. Christopher Ehmann, Judith Feinberg, Bharat Nathwani, Parkash S. Gill, Ron Mitsuyasu
Journal: JAMA (1991)

<h3>Objective.</h3> —To ascertain if low-dose multiagent chemotherapy, with central nervous system prophylaxis and antiretroviral therapy, might be associated with increased efficacy and decreased risk of intercurrent infection in patients with malignant lymphoma related to the acquired immunodeficiency syndrome (AIDS). <h3>Design.</h3> —A phase II prospective clinical trial, with median follow-up of 33 months. <h3>Setting.</h3> —Eight university hospitals, within the context of the AIDS Clinical Trials Units, sponsored by the National Institute of Allergy and Infectious Diseases. <h3>Patients.</h3> —Forty-two patients with AIDS-related malignant lymphoma. All were evaluable for toxicity assessment, and 35 for response. <h3>Intervention.</h3> —A low-dose modification of the M-BACOD regimen (day 1): cyclophosphamide, 300 mg/m<sup>2</sup>intravenously (IV); doxorubicin, 25 mg/m<sup>2</sup>IV; vincristine sulfate, 1.4 mg/m<sup>2</sup>IV; bleomycin, 4 mg/m<sup>2</sup>IV; dexamethasone, 3 mg/m<sup>2</sup>orally on days 1 through 5; methotrexate, 500 mg/m<sup>2</sup>IV on day 15, with leucovorin rescue. Intrathecal cytosine arabinoside (50 mg) to all on days 1, 8, 21, and 28, with radiation therapy to a helmet field to those with central nervous system involvement. Zidovudine for 12 months after completion of four to six cycles of chemotherapy. <h3>Main Outcome Measures.</h3> —Response rate and number of opportunistic infections. <h3>Results.</h3> —Response rate was 51% with a complete response of 46%. Of 16 complete responses, relapse occurred in four, none isolated to the central nervous system. Opportunistic infections occurred in 21% of those receiving treatment. Median duration of survival among all 42 patients is 5.6 months, 6.5 months in 35 patients evaluable for response, and 15 months in patients with complete response. Lower concentration of CD4 cells, history of prior AIDS, bone marrow involvement, and stage IV disease were independently associated with decreased survival. <h3>Conclusions.</h3> —Low-dose chemotherapy with central nervous system prophylaxis and zidovudine maintenance may be associated with durable remissions in AIDS-related lymphoma with fewer opportunistic infections than noted in prior reports. (<i>JAMA</i>. 1991;266:84-88)
Expression of the mdr (P-glycoprotein) Gene in Chinese Hamster Digestive Tracts1
Authors: T. Mukhopadhyay, J. G. Batsakis, M. T. Kuo
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Expression of the mdr (P-glycoprotein) Gene in Chinese Hamster Digestive Tracts1 Get access Tapas Mukhopadhyay, Tapas Mukhopadhyay Search for other works by this author on: Oxford Academic PubMed Google Scholar John G. Batsakis, John G. Batsakis Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Tien Kuo M. Tien Kuo * 3Department of Molecular Pathology, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor InstututeHousion, TX 77030. *Correspondence to: Dr. M. Tien Kuo, Department of Molecular Pathology-85, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, 1515 Holcombe Ave., Houston, TX 77030. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 4, 20 April 1988, Pages 269–275, https://doi.org/10.1093/jnci/80.4.269 Published: 20 April 1988 Article history Received: 17 November 1987 Revision received: 14 December 1987 Accepted: 17 December 1987 Published: 20 April 1988
Breast cancer 1 (BRCA1) protein expression as a prognostic marker in sporadic epithelial ovarian carcinoma: an NCIC CTG OV.16 correlative study
Authors: J.I. Weberpals, D. Tu, J.A. Squire, M.S. Amin, S. Islam, L.B. Pelletier, A.M. O'Brien, P.J. Hoskins, E.A. Eisenhauer
Journal: Annals of Oncology (2011)
GIN Transposons: Genetic Elements Linking Retrotransposons and Genes
Authors: I. Marin
Journal: Molecular Biology and Evolution (2010)

In a previous work, we characterized a gene, called Gypsy Integrase 1 (GIN1), which encodes a protein very similar to the integrase domains present in Gypsy/Ty3 retrotransposons. I describe here a paralog of GIN1 and GIN2 and show that both genes are present in multiple vertebrates and that a likely homolog is found in urochordates. Surprisingly, phylogenetic and structural analyses support the counterintuitive idea that the GIN genes did not directly derive from retrotransposons but from a novel type of animal-specific DNA transposons, the GIN elements. These elements, described for the first time in this study, are characterized by containing a gene that encodes a protein that is also very similar to Gypsy/Ty3 integrases. It turns out that the sequences of the integrases encoded by GIN1 and GIN2 are more similar to those found in GIN elements than to those detected in retrotransposons. Moreover, several introns are in the same positions in the integrase-encoding genes of some GIN elements, GIN1 and GIN2. The simplest explanation for these results is that GIN elements appeared early in animal evolution by co-option of the integrase of a retrotransposon, they later expanded in multiple animal lineages, and, eventually, gave rise to the GIN genes. In summary, GIN transposons may be the “missing link” that explain how GIN genes evolved from retrotransposons. GIN1 and GIN2 may have contributed to control the expansion of GIN elements and Gypsy/Ty3 retrotransposons in chordates.
Cortical Blindness and Homonymous Hemianopia in the Postpartum Period
Authors: M. Flint Beal
Journal: JAMA (1980)

CEREBRAL venous thrombosis is a known complication of the puerperium. Cortical blindness has not been reported as a sole manifestation of this syndrome. We describe one patient with cortical blindness and two with homonymous hemianopia attributed to puerperal cerebral venous thrombosis. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 28-year-old woman had development of a severe occipital headache immediately after an uneventful pregnancy and delivery. Four days later, she was unable to see when she awoke from a nap and experienced the first of three typical grand mal seizures. Her history included a severe left-sided throbbing headache five years earlier, which had been preceded by five minutes of partial loss of vision with "spots and wavy lines." Findings from general physical examination with special attention to the optic fundi were normal. The pupils reacted briskly and symmetrically to light. There was no perception of light or motion, and opticokinetic nystagmus was absent.
Survey of flexible fibreoptic bronchoscopy in the UK
Authors: D. Honeybourne
Journal: European Respiratory Journal (2002)

To the Editor: 

The survey of flexible fibreoptic bronchoscopy in the United Kingom by Smyth and Stead 1 was based on a questionnaire and is therefore completely reliant on the memories' of physicians who have carried out bronchoscopies. Unfortunately, it quotes guidelines that are out of date and indeed does not reference the latest British Thoracic Society guidelines which were published 9 months before the paper was accepted for publication 2. The survey had a modest response rate of 60%, but nevertheless there were some interesting …
Occult hepatitis B virus infection in hematopoietic stem cell donors in a hepatitis B virus endemic area
Authors: Chee-kin Hui, Jian Sun, Wing-yan Au, Albert K.W. Lie, Yui-hung Yueng, Hai-ying Zhang, Nikki P. Lee, Jin-ling Hou, Raymond Liang, George K.K. Lau
Journal: Journal of Hepatology (2005)
Regulation of bovine endothelial constitutive nitric oxide synthase by oxygen.
Authors: J K Liao, J J Zulueta, F S Yu, H B Peng, C G Cote, P M Hassoun
Journal: Journal of Clinical Investigation (1995)

Oxygen (O2) may regulate pulmonary vascular resistance through changes in endothelial nitric oxide (NO) production. To determine whether constitutive NO synthase (cNOS) is regulated by O2, we assessed cNOS expression and activity in bovine pulmonary artery endothelial cells exposed to different concentrations of O2. In a time-dependent manner, changes in O2 concentration from 95 to 3% produced a progressive decrease in cNOS mRNA and protein levels resulting in 4.8- and 4.3-fold reductions after 24h, respectively. This correlated with changes in cNOS activity as determined by nitrite measurements. Compared with 20% O2, cNOS activity was increased 1.5-fold in 95% O2 and decreased 1.9-fold in 3% O2. A decrease in O2 concentration from 94 to 3% shortened cNOS mRNA half-life from 46 to 24 h and caused a 20-fold repression of cNOS gene transcription. Treatment with cycloheximide produced a threefold increase in cNOS mRNA at all O2 concentrations, suggesting that cNOS mRNA expression is negatively regulated under basal condition. We conclude that O2 upregulates cNOS expression through transcriptional and post-transcriptional mechanisms. A decrease in cNOS activity in the presence of low O2 levels, therefore, may contribute to hypoxia-induced vasoconstriction in the pulmonary circulation.
Exercise induced critical ischaemia of the upper limb secondary to a cervical rib
Authors: R G Casey, S Richards, M O’Donohoe
Journal: British Journal of Sports Medicine (2003)

The case is reported of a 32 year old woman with acute on chronic upper limb ischaemia due to thrombus from a cervical rib that had compressed the right subclavian artery of her dominant hand after use of a rowing machine. If not detected early, this condition can be debilitating especially in the young. A multidisciplinary approach is advisable to ensure a satisfactory outcome.
Differential expression patterns of matrix metalloproteinases and their inhibitors during development of osteoarthritis in a transgenic mouse model
Authors: H J Salminen
Journal: Annals of the Rheumatic Diseases (2002)

To characterise the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) during degeneration of articular cartilage in a transgenic Del1 mouse model for osteoarthritis.Northern analysis was used to measure mRNA levels of MMP-2, -3, -8, -9, -13, and -14, and TIMP-1, -2, and -3 in total RNA extracted from knee joints of transgenic Del1 mice, harbouring a 15 amino acid deletion in the triple helical domain of the alpha1(II) collagen chain, using their non-transgenic littermates as controls. Immunohistochemistry was used to study the presence of cleavage products (neoepitopes) of type II collagen, and the distribution of MMP-13 and TIMP-1 in degenerating cartilage.Each of the MMP and TIMP mRNAs analysed exhibited distinct expression patterns during development and osteoarthritic degeneration of the knee joint. The most striking change was up regulation of MMP-13 mRNA expression in the knee joints of Del1 mice at the onset of cartilage degeneration. However, the strongest immunostaining for MMP-13 and its inhibitor TIMP-1 was not seen in the degenerating articular cartilage but in synovial tissue, deep calcified cartilage, and subchondral bone. The localisation of type II collagen neoepitopes in chondrocytes and their pericellular matrix followed a similar pattern; they were not seen in cartilage fibrillations, but in adjacent unaffected cartilage.The primary localisation of MMP-13 and TIMP-1 in hyperplastic synovial tissue, subchondral bone, and calcified cartilage suggests that up regulation of MMP-13 expression during early degeneration of articular cartilage is a secondary response to cartilage erosion. This interpretation is supported by the distribution of type II collagen neoepitopes. Synovial production of MMP-13 may be related to removal of tissue debris released from articular cartilage. In the deep calcified cartilage and adjacent subchondral bone, MMP-13 probably participates in tissue remodelling.
MDA-9/syntenin is a key regulator of glioma pathogenesis
Authors: Timothy P. Kegelman, Swadesh K. Das, Bin Hu, Manny D. Bacolod, Christine E. Fuller, Mitchell E. Menezes, Luni Emdad, Santanu Dasgupta, Albert S. Baldwin, Jeffrey N. Bruce, Paul Dent, Maurizio Pellecchia, Devanand Sarkar, Paul B. Fisher
Journal: Neuro-Oncology (2013)

The extraordinary invasiveness of human glioblastoma multiforme (GBM) contributes to treatment failure and the grim prognosis of patients diagnosed with this tumor. Consequently, it is imperative to define further the cellular mechanisms that control GBM invasion and identify promising novel therapeutic targets. Melanoma differentiation associated gene–9 (MDA-9/syntenin) is a highly conserved PDZ domain–containing scaffolding protein that promotes invasion and metastasis in vitro and in vivo in human melanoma models. To determine whether MDA-9/syntenin is a relevant target in GBM, we investigated its expression in tumor samples and involvement in GBM invasion and angiogenesis. We assessed MDA-9/syntenin levels in available databases, patient tumor samples, and human-derived cell lines. Through gain-of-function and loss-of-function studies, we analyzed changes in invasion, angiogenesis, and signaling in vitro. We used orthotopic xenografts with GBM6 cells to demonstrate the role of MDA-9/syntenin in GBM pathogenesis in vivo. MDA-9/syntenin expression in high-grade astrocytomas is significantly higher than normal tissue counterparts. Forced overexpression of MDA-9/syntenin enhanced Matrigel invasion, while knockdown inhibited invasion, migration, and anchorage-independent growth in soft agar. Moreover, overexpression of MDA-9/syntenin increased activation of c-Src, p38 mitogen-activated protein kinase, and nuclear factor kappa-B, leading to elevated expression of matrix metalloproteinase 2 and secretion of interleukin-8 with corresponding changes observed upon knockdown. GBM6 cells that stably express small hairpin RNA for MDA-9/syntenin formed smaller tumors and had a less invasive phenotype in vivo. Our findings indicate that MDA-9/syntenin is a novel and important mediator of invasion in GBM and a key regulator of pathogenesis, and we identify it as a potential target for anti-invasive treatment in human astrocytoma.
Juvenile-onset systemic lupus erythematosus: different clinical and serological pattern than adult-onset systemic lupus erythematosus
Authors: I E A Hoffman, B R Lauwerys, F De Keyser, T W J Huizinga, D Isenberg, L Cebecauer, J Dehoorne, R Joos, G Hendrickx, F Houssiau, D Elewaut
Journal: Annals of the Rheumatic Diseases (2008)

To investigate differences in clinical signs and symptoms, and in antinuclear antibodies (ANA), between patients with juvenile-onset and adult-onset systemic lupus erythematosus (SLE).Clinical and serological data of 56 patients with juvenile-onset SLE were compared with data of 194 patients with adult-onset SLE. ANA were determined by line immunoassay and by indirect immunofluorescence on Crithidia luciliae.Renal involvement, encephalopathy and haemolytic anaemia were seen, and anti-dsDNA, anti-ribosomal P and antihistone antibodies found, significantly more often in juvenile-onset SLE. Anti-dsDNA antibodies were directly associated, and anti-ribosomal P antibodies inversely associated, with renal involvement in juvenile-onset SLE. In juvenile patients with SLE and anti-dsDNA and without anti-ribosomal P antibodies the odds ratio for glomerulonephritis was 9.00; no patients with anti-ribosomal P but without anti-dsDNA had renal involvement.Patients with juvenile-onset SLE more often have renal involvement and encephalopathy than patients with adult-onset SLE. Anti-ribosomal P, anti-dsDNA and antihistone antibodies are more often found in patients with juvenile-onset SLE.
Smoking reduction and the rate of decline in FEV1: results from the Lung Health Study
Authors: M. S. Simmons, J. E. Connett, M. A. Nides, P. G. Lindgren, E. C. Kleerup, R. P. Murray, W. M. Bjornson, D. P. Tashkin
Journal: European Respiratory Journal (2005)

Previous findings from the Lung Health Study have shown that smoking cessation and sustained abstinence substantially reduce the rate of decline in forced expiratory volume (FEV 1 ) among smokers with early chronic obstructive pulmonary disease (COPD) when compared with continuing smoking. Intermittent quitters demonstrated rates of FEV 1 decline intermediate between those of sustained quitters and continuing smokers. In this study, data from 1,980 participants were analysed from 10 centres of the Lung Health Study in the USA and Canada. All participants were smokers with mild-to-moderate COPD who were unable to quit smoking at any time during the 1st yr of the study. No linear relationship was found between reduction in cigarettes per day and changes in FEV 1 during the 1st yr of the study. However, examination of the data revealed that this relationship was nonlinear. Further analysis found that smokers who reduced their cigarettes per day to very low amounts had smaller declines in FEV 1 than those who did not. Reduction in cigarettes per day was associated with only minimal changes in the presence of chronic respiratory symptoms. In conclusion, compensatory changes in smoking behaviour may account for the limited and unpredictable impact of smoking reduction on lung function decline and symptom prevalence when compared with smoking cessation.
Renal Phosphate Wasting in the Absence of Adenylyl Cyclase 6
Authors: Robert A. Fenton, Fiona Murray, Jessica A. Dominguez Rieg, Tong Tang, Moshe Levi, Timo Rieg
Journal: Journal of the American Society of Nephrology (2014)

Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) enhance phosphate excretion by the proximal tubule of the kidney by retrieval of the sodium-dependent phosphate transporters (Npt2a and Npt2c) from the apical plasma membrane. PTH activates adenylyl cyclase (AC) through PTH 1 receptors and stimulates the cAMP/PKA signaling pathway. However, the precise role and isoform(s) of AC in phosphate homeostasis are not known. We report here that mice lacking AC6 (AC6(-/-)) have increased plasma PTH and FGF-23 levels compared with wild-type (WT) mice but comparable plasma phosphate concentrations. Acute activation of the calcium-sensing receptor or feeding a zero phosphate diet almost completely suppressed plasma PTH levels in both AC6(-/-) and WT mice, indicating a secondary cause for hyperparathyroidism. Pharmacologic blockade of FGF receptors resulted in a comparable increase in plasma phosphate between genotypes, whereas urinary phosphate remained significantly higher in AC6(-/-) mice. Compared with WT mice, AC6(-/-) mice had reduced renal Npt2a and Npt2c protein abundance, with approximately 80% of Npt2a residing in lysosomes. WT mice responded to exogenous PTH with redistribution of Npt2a from proximal tubule microvilli to intracellular compartments and lysosomes alongside a PTH-induced dose-response relationship for fractional phosphate excretion and urinary cAMP excretion. These responses were absent in AC6(-/-) mice. In conclusion, AC6 in the proximal tubule modulates cAMP formation, Npt2a trafficking, and urinary phosphate excretion, which are highlighted by renal phosphate wasting in AC6(-/-) mice.
Decreased methionine synthesis in purine nucleoside-treated T and B lymphoblasts and reversal by homocysteine.
Authors: G R Boss, R B Pilz
Journal: Journal of Clinical Investigation (1984)

Purine nucleosides, which accumulate in adenosine deaminase and purine nucleoside phosphorylase deficiency, are toxic to lymphoid cells. Since adenine nucleosides inhibit S-adenosylhomocysteine hydrolase, they could potentially decrease intracellular methionine synthesis. To test this hypothesis, we measured methionine synthesis by the use of [14C]formate as a radioactive precursor in cultured human T and B lymphoblasts treated with varying concentrations of purine nucleosides; 2'-deoxycoformycin and 8-aminoguanosine were added to inhibit adenosine deaminase and purine nucleoside phosphorylase, respectively. In the T lymphoblasts methionine synthesis was inhibited approximately 50% by 10 microM of 2'-deoxyadenosine, adenine arabinoside, or 2'-deoxyguanosine. By contrast, in the B lymphoblasts methionine synthesis was considerably less affected by these nucleosides, with 50% inhibition occurring at 100 microM of 2'-deoxyadenosine and adenine arabinoside; 100 microM of 2'-deoxyguanosine yielded less than 10% inhibition. Adenosine and guanosine were considerably less potent inhibitors of methionine synthesis in both the T and B lymphoblasts. An adenosine deaminase-deficient and a purine nucleoside phosphorylase-deficient cell line, both of B cell origin, exhibited sensitivities to the nucleosides similar to those of the normal B cell lines. In both the T and B cell lines homocysteine reversed the methionine synthesis inhibition induced by the adenine nucleosides and guanosine and largely reversed that induced by 2'-deoxyguanosine. Methionine synthesis from homocysteine generates free tetrahydrofolate from 5-methyltetrahydrofolate, the main intracellular storage form of folate. We conclude that purine nucleoside toxicity may be partly mediated through (a) decreased intracellular methionine synthesis, and (b) altered folate metabolism.
Information theory: The Holy Grail of cortical computation?
Authors: James V. Stone
Journal: Behavioral and Brain Sciences (1997)

Simple hypotheses are intrinsically attractive, and, for this reason, need to be formulated with utmost precision if they are to be testable. Unfortunately, it is hard to see how Phillips &amp; Singer's hypothesis might be unambiguously refuted. Despite this, the authors have provided much evidence consistent with the hypothesis, and have proposed a natural and powerful extension for information theoretic approaches to learning.