tbuckley/cabot-search huggingface dataset:
MDR Tuberculosis — Critical Steps for Prevention and Control
Authors: Eva Nathanson, Paul Nunn, Mukund Uplekar, Katherine Floyd, Ernesto Jaramillo, Knut Lönnroth, Diana Weil, Mario Raviglione
Journal: New England Journal of Medicine (2010)

ultidrug-resistant (MDR) tuberculosis is defined as disease caused by strains of Mycobacterium tuberculosis that are at least resistant to treatment with isoniazid and rifampicin; extensively drug-resistant (XDR) tuberculosis refers to disease caused by multidrug-resistant strains that are also resistant to treatment with any fluoroquinolone and any of the injectable drugs used in treatment with second-line anti-tuberculosis drugs (amikacin, capreomycin, and kanamycin).MDR tuberculosis and XDR tuberculosis are serious threats to the progress that has been made in the control of tuberculosis worldwide over the past decade. 1,2 In 2008, an estimated 440,000 cases of MDR tuberculosis emerged globally. 1India and China carry the greatest estimated burden of MDR tuberculosis, together accounting for almost 50% of the world's total cases.More than three quarters of the estimated cases of MDR tuberculosis occur in previously untreated patients.The proportion of MDR cases among new cases and previously treated cases of tuberculosis reported globally from 1994 through 2009 ranged from 0 to 28.3% and from 0 to 61.6%, respectively (Fig. 1).The highest proportions of MDR cases, and the most severe drug-resistance patterns, appear in the countries of the former Soviet Union.By 2009, a total of 58 countries had reported at least one case of XDR tuberculosis.In eight countries, reported cases of XDR tuberculosis account for more than 10% of all cases of MDR tuberculosis, and six of these countries were part of the former Soviet Union.By far the largest number of cases of XDR tuberculosis has been reported from South Africa (10.5% of all cases of MDR tuberculosis in that country), owing to rapid spread among people infected with the human immunodeficiency virus (HIV).National programs are failing to diagnose and treat MDR tuberculosis.Globally, just under 30,000 cases of MDR tuberculosis were reported to the World Health Organization (WHO) in 2008 (7% of the estimated total), of which less than one fifth were managed according to international guidelines.The vast majority of the remaining cases probably are not diagnosed or, if diagnosed, are mismanaged.This problem remains despite the evidence that management of MDR tuberculosis is cost-effective 3 and that treatment of MDR tuberculosis, and even treatment of XDR tuberculosis, is feasible in persons who are not infected with HIV. 4,5 In some countries, the incidence of tuberculosis is rising, and the incidence of MDR tuberculosis appears to be rising even faster (e.g., in Botswana and South Korea). 6However, in Estonia, Hong Kong, the United States, and Orel and Tomsk Oblasts (in the Russian Federation), the incidence of tuberculosis is falling, and the incidence of MDR tuberculosis appears to be falling even faster. 1,6 This trend is
Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets
Authors: Claude Sportès, Frances T. Hakim, Sarfraz A. Memon, Hua Zhang, Kevin S. Chua, Margaret R. Brown, Thomas A. Fleisher, Michael C. Krumlauf, Rebecca R. Babb, Catherine K. Chow, Terry J. Fry, Julie Engels, Renaud Buffet, Michel Morre, Robert J. Amato, David J. Venzon, Robert Korngold, Andrew Pecora, Ronald E. Gress, Crystal L. Mackall
Journal: The Journal of Experimental Medicine (2008)

Interleukin-7 (IL-7) is a homeostatic cytokine for resting T cells with increasing serum and tissue levels during T cell depletion. In preclinical studies, IL-7 therapy exerts marked stimulating effects on T cell immune reconstitution in mice and primates. First-in-human clinical studies of recombinant human IL-7 (rhIL-7) provided the opportunity to investigate the effects of IL-7 therapy on lymphocytes in vivo. rhIL-7 induced in vivo T cell cycling, bcl-2 up-regulation, and a sustained increase in peripheral blood CD4+ and CD8+ T cells. This T cell expansion caused a significant broadening of circulating T cell receptor (TCR) repertoire diversity independent of the subjects' age as naive T cells, including recent thymic emigrants (RTEs), expanded preferentially, whereas the proportions of regulatory T (T reg) cells and senescent CD8+ effectors diminished. The resulting composition of the circulating T cell pool more closely resembled that seen earlier in life. This profile, distinctive among cytokines under clinical development, suggests that rhIL-7 therapy could enhance and broaden immune responses, particularly in individuals with limited naive T cells and diminished TCR repertoire diversity, as occurs after physiological (age), pathological (human immunodeficiency virus), or iatrogenic (chemotherapy) lymphocyte depletion.
Advances in Light Microscopy for Neuroscience
Authors: Brian A. Wilt, Laurie D. Burns, Eric Tatt Wei Ho, Kunal K. Ghosh, Eran A. Mukamel, Mark J. Schnitzer
Journal: Annual Review of Neuroscience (2009)

Since the work of Golgi and Cajal, light microscopy has remained a key tool for neuroscientists to observe cellular properties. Ongoing advances have enabled new experimental capabilities using light to inspect the nervous system across multiple spatial scales, including ultrastructural scales finer than the optical diffraction limit. Other progress permits functional imaging at faster speeds, at greater depths in brain tissue, and over larger tissue volumes than previously possible. Portable, miniaturized fluorescence microscopes now allow brain imaging in freely behaving mice. Complementary progress on animal preparations has enabled imaging in head-restrained behaving animals, as well as time-lapse microscopy studies in the brains of live subjects. Mouse genetic approaches permit mosaic and inducible fluorescence-labeling strategies, whereas intrinsic contrast mechanisms allow in vivo imaging of animals and humans without use of exogenous markers. This review surveys such advances and highlights emerging capabilities of particular interest to neuroscientists.
Fas and Fas-Associated Death Domain Protein Regulate Monocyte Chemoattractant Protein-1 Expression by Human Smooth Muscle Cells Through Caspase- and Calpain-Dependent Release of Interleukin-1α
Authors: Friedemann J. Schaub, W. Conrad Liles, Nicola Ferri, Kirsten Sayson, Ronald A. Seifert, Daniel F. Bowen-Pope
Journal: Circulation Research (2003)

We previously reported that treatment of human vascular smooth muscle cells (SMCs) with proapoptotic stimuli, including Fas ligand plus cycloheximide (FasL/Chx), or overexpression of Fas-associated death domain protein (FADD) result in increased expression of monocyte chemoattractant protein-1 (MCP-1) and other proinflammatory genes. In this study, we demonstrate that Fas/FADD-induced MCP-1 upregulation is driven by an autocrine/paracrine signaling loop in which interleukin (IL)-1alpha synthesis and release are activated through caspase- and calpain-dependent processes. Untreated SMCs contain very little IL-1alpha protein or transcript. Both were increased greatly in response to Fas/FADD activation, primarily through an autocrine/paracrine pathway in which secreted IL-1alpha stimulated additional IL-1alpha synthesis and release. Caspase 8 (Csp8) activity increased in response to FasL/Chx treatment, and Csp8 inhibitors markedly reduced IL-1alpha release and MCP-1 upregulation. In contrast, Csp8 activity was not significantly increased in response to FADD overexpression and caspase inhibitors did not effect FADD-induced MCP-1 upregulation. Both FasL/Chx treatment and FADD overexpression increased the activity of calpains. Calpain inhibitors reduced IL-1alpha release and MCP-1 upregulation in both FADD-overexpressing SMCs and FasL/Chx-treated SMCs without blocking Csp8 activity. This indicates that calpains are not required for activation of caspases and that caspase activation is not sufficient for IL-1alpha release and MCP-1 upregulation. These data suggest that calpains play a dominant role in Fas/FADD-induced IL-1alpha release and MCP-1 upregulation and that caspase activation may function to amplify the effects of calpain activation.
Assessment of Care by Breast Cancer Patients Participating or Not Participating in a Randomized Controlled Trial: A Report With the Patients' Committee for Clinical Trials of the Ligue Nationale Contre le Cancer
Authors: Claire Julian-Reynier, Jean Genève, Florence Dalenc, Dominique Genre, Alain Monnier, Pierre Kerbrat, Rémy Largillier, Daniel Serin, Maria Rios, Henri Roché, Marta Jimenez, Carole Tarpin, Dominique Maraninchi
Journal: Journal of Clinical Oncology (2007)

Cancer patients participating in randomized controlled trials (RCTs) have not been found to have better clinical outcomes than other patients. Our objective was to assess the impact of RCTs on patients' satisfaction with care.A prospective study was carried out in a cohort of women with breast cancer (N = 455) divided into those invited to participate in an RCT (201 acceptances, 66 refusals) and a comparable control group not invited to participate (n = 188). All the patients underwent the same treatment (fluorouracil, epirubicin, and cyclophosphamide 100 mg/m2 for six cycles). One and 7 months after the beginning of chemotherapy, self-administered satisfaction scores were used to compare the women's assessment of their care (Comprehensive Assessment of Satisfaction with Care validated scale).At the beginning of chemotherapy, women to whom RCT had been proposed rated the doctors' availability (average +/- standard deviation [SD]: RCT acceptance group, 3.60 +/- 0.78; RCT refusal group, 3.68 +/- 0.87; control group, 3.41 +/- 0.82; P < or = .02) and the doctors' communication (average +/- SD: RCT acceptance group, 3.56 +/- 0.88; RCT refusal group, 3.67 +/- 0.88; control group, 3.39 +/- 0.84; P .05) higher than those to whom the trial was not proposed. After the treatment, participants in the RCT felt that their doctor was more supportive (average +/- SD: RCT acceptance group, 3.04 +/- 0.92; control group, 2.77 +/- 0.85; P = .005) and more informative about their illness and treatment (average +/- SD: RCT acceptance group, 3.34 +/- 0.88; control group, 3.08 +/- 0.92; P = .006) than those in the control group. The general level of satisfaction was also higher in the RCT acceptance group.Women participating in an RCT have a more positive picture of their doctors' care than others, probably because of the structural effects of the informed consent and data collection processes.
Dilemmas of rationality
Authors: K. I. Manktelow
Journal: Behavioral and Brain Sciences (2000)

This commentary focuses on the implications of practical reasoning research for the view of rationality in Stanovich &amp; West's target article. Practical reasoning does not correlate with intelligence or other reasoning tasks. Explanation in decision making terms raises the issue of dilemmas, making it hard to specify the correct norm, when an action can satisfy or conflict with two equally justifiable goals.
Conjugation of immunostimulatory DNA to the short ragweed allergen Amb a 1 enhances its immunogenicity and reduces its allergenicity
Authors: Helen Tighe, Kenji Takabayashi, David Schwartz, Gary Van Nest, Stephen Tuck, Joseph J. Eiden, Anne Kagey-Sobotka, Peter S. Creticos, Lawrence M. Lichtenstein, Hans L. Spiegelberg, Eyal Raz
Journal: Journal of Allergy and Clinical Immunology (2000)
Regulation of GPCRs by Endocytic Membrane Trafficking and Its Potential Implications
Authors: Aylin C. Hanyaloglu, Mark von Zastrow
Journal: The Annual Review of Pharmacology and Toxicology (2007)

The endocytic pathway tightly controls the activity of G protein-coupled receptors (GPCRs). Ligand-induced endocytosis can drive receptors into divergent lysosomal and recycling pathways, producing essentially opposite effects on the strength and duration of cellular signaling via heterotrimeric G proteins, and may also promote distinct signaling events from intracellular membranes. This chapter reviews recent developments toward understanding the molecular machinery and functional implications of GPCR sorting in the endocytic pathway, focusing on mammalian GPCRs whose ligand-induced endocytosis is mediated primarily by clathrin-coated pits. Lysosomal sorting of a number of GPCRs occurs via a highly conserved mechanism requiring covalent tagging of receptors with ubiquitin. There is increasing evidence that additional, noncovalent mechanisms control the sorting of endocytosed GPCRs to lysosomes in mammalian cells. Recycling of several GPCRs to the plasma membrane is also specifically sorted, via a mechanism requiring both receptor-specific and shared sorting proteins. The current data reveal an unprecedented degree of specificity and plasticity in the cellular regulation of mammalian GPCRs by endocytic membrane trafficking. These developments have fundamental implications for GPCR pharmacology, and suggest new mechanisms that could be exploited in GPCR-directed pharmacotherapy.
Direct amplification of Mycobacterium tuberculosis deoxyribonucleic acid in paucibacillary tuberculosis
Authors: C Saltini
Journal: European Respiratory Journal (1998)

The discovery of the polymerase chain reaction (PCR)as a means to generate detectable signals from as little asa single molecule of target deoxyribonucleic acid (DNA)[1] has led to the development of extremely powerful andrapid diagnostic tests for a number of infectious agents.PCR was therefore expected to improve significantly thesensitivity of tests for the diagnosis of tuberculosis (TB),compared with the standard stains for acid fast bacilli(AFB) on sputum smears. Since the first report by H
T lymphocytes from patients with primary biliary cirrhosis produce reduced amounts of lymphotoxin, tumor necrosis factor and interferon-γ upon mitogen stimulation
Authors: Ulrich Spengler, Achim Möller, Maria C. Jung, Gerald Messer, Reinhart Zachoval, Robert M. Hoffmann, Josef Eisenburg, Gustav Paumgartner, Gert Riethmüller, Elisabeth H. Weiss, Gerd R. Pape
Journal: Journal of Hepatology (1992)
THE CYTOLOGICAL DISTRIBUTION IN PIGEON SKELETAL MUSCLE OF ENZYMES ACTING ON PHOSPHORYLATED NUCLEOTIDES
Authors: Amara Kitiyakara, John W. Harman
Journal: The Journal of Experimental Medicine (1953)

A procedure has been described for the centrifugal fractionation of the cytological components of pigeon breast muscle. An analysis of the distribution of enzyme activity among the different particles reveals a predominant location of magnesium-activated ATPase and myokinase in the cytochondria. The myofibrillar nuclear components are the site of calcium-activated ATPase and adenylic acid deaminase.
The role of vascular endothelial growth factor D in diagnosis of polycystic lung diseases
Authors: Elzbieta Radzikowska, Paulina Jagus, Agnieszaka Skoczylas, Joanna Chorostowska-Wynimko, Elzbieta Wiatr, Kazimierz Roszkowski-Sliz
Journal: European Respiratory Journal (2013)

The study was aimed at determining the prospective discriminative value of serum vascular endothelial growth factor D (VEGF-D) concentration in reliable diagnostic differentiation of patients with lymphangioleimyomatosis (LAM) from subjects with other polycystic lung diseases (PLD).  Methods: Serum VEGF-D level was measured by enzyme-linked immunoassay in 37 patients with PLD including 8 women with LAM, 27 patients (13 women and 14 men) with pulmonary Langerhans cell histiocytosis (PLCH), 1 woman with lymphocytic interstitial pneumonia (LIP) and 1 woman with tuberous sclerosis (TSC) without LAM.  Results: Serum VEGF-D concentration was significantly higher in LAM patients [median 1979 pg/ml (interquartile range (IQR) 468-3897pg/ml) in comparison to subjects with PLCH [median 534pg/ml (interquartile range (IQR) 126-791pg/ml], TSC without LAM-387pg/ml and LIP-233pg/ml.  The VEGF-D cut-off level of 790 pg/ml provided significantly discriminative consistency for LAM diagnosis with specificity of 96.3% and sensitivity of 87,5%.  Conclusions: A serum VEGF-D level exceeding 790 pg/ml in a woman with typical cystic changes on high-resolution computer tomography (HRCT) scans is diagnostically specific for LAM.
Lymphoma Occurring During Pregnancy: Antenatal Therapy, Complications, and Maternal Survival in a Multicenter Analysis
Authors: Andrew M. Evens, Ranjana Advani, Oliver W. Press, Izidore S. Lossos, Julie M. Vose, Francisco J. Hernandez-Ilizaliturri, Barrett K. Robinson, Stavroula Otis, Liat Nadav Dagan, Ramsey Abdallah, Aimee Kroll-Desrosiers, Jessica L. Yarber, Jose Sandoval, Kelley Foyil, Linda M. Parker, Leo I. Gordon, Kristie A. Blum, Christopher R. Flowers, John P. Leonard, Thomas M. Habermann, Nancy L. Bartlett
Journal: Journal of Clinical Oncology (2013)

Lymphoma is the fourth most frequent cancer in pregnancy; however, current clinical practice is based largely on small series and case reports.In a multicenter retrospective analysis, we examined treatment, complications, and outcomes for Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) occurring during pregnancy.Among 90 patients (NHL, n = 50; HL, n = 40), median age was 30 years (range, 18 to 44 years) and median diagnosis occurred at 24 weeks gestation. Of patients with NHL, 52% had advanced-stage versus 25% of patients with HL (P = .01). Pregnancy was terminated in six patients. Among the other 84 patients, 28 (33%) had therapy deferred to postpartum; these patients were diagnosed at a median 30 weeks gestation. This compared with 56 patients (67%) who received antenatal therapy with median lymphoma diagnosis at 21 weeks (P < .001); 89% of these patients received combination chemotherapy. The most common preterm complication was induction of labor (33%). Gestation went to full term in 56% of patients with delivery occurring at a median of 37 weeks. There were no differences in maternal complications, perinatal events, or median infant birth weight based on deferred versus antenatal therapy. At 41 months, 3-year progression-free survival (PFS) and overall survival (OS) for NHL were 53% and 82%, respectively, and 85% and 97%, respectively, for HL. On univariate analysis for NHL, radiotherapy predicted inferior PFS, and increased lactate dehydrogenase and poor Eastern Cooperative Oncology Group performance status (ECOG PS) portended worse OS. For HL patients, nulliparous status and "B" symptoms predicted inferior PFS.Standard (non-antimetabolite) combination chemotherapy administered past the first trimester, as early as 13 weeks gestation, was associated with few complications and expected maternal survival with lymphoma occurring during pregnancy.
Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma
Authors: W. Weder, R.A. Stahel, J. Bernhard, S. Bodis, P. Vogt, P. Ballabeni, D. Lardinois, D. Betticher, R. Schmid, R. Stupp, H.B. Ris, M. Jermann, W. Mingrone, A.D. Roth, A. Spiliopoulos
Journal: Annals of Oncology (2007)
EPIDEMIOLOGY OF OPHTHALMIA NEONATORUM IN KENYA
Authors: Marie Laga, Herbert Nzanze, RobertC Brunham, Gregory Maitha, LourdesJ.D D'Costa, J.K Mati, Mary Cheang, FrancisA Plummer, Warren Namaara, J.O Ndinya-Achola, AllanR Ronald, V.B Bhullar, Lieve Fransen, Peter Piot
Journal: The Lancet (1986)
Basal lamina disorganisation of the acini and ducts of labial salivary glands from patients with Sjogren's syndrome: association with mononuclear cell infiltration
Authors: C Molina
Journal: Annals of the Rheumatic Diseases (2005)

<h3>Abstract</h3> Parkinsonism is a feature of several neurodegenerative disorders, including Parkinson’s disease (PD), progressive supranuclear palsy (PSP), corticobasal degeneration syndrome (CBS) and multiple system atrophy (MSA). Neuroimaging studies have yielded insights into parkinsonism; however it remains unclear whether there is a common neural substrate amongst disorders. The aim of the present meta-analysis was to identify consistent brain alterations in parkinsonian disorders (PD, PSP, CBS, MSA) both individually, and combined, to elucidate the shared substrate of parkinsonism. 33,505 studies were systematically screened following searches of MEDLINE Complete and Embase databases. A series of whole-brain activation likelihood estimation meta-analyses were performed on 126 neuroimaging studies (64 PD; 25 PSP; 18 CBS; 19 MSA) utilizing anatomical MRI, perfusion or metabolism positron emission tomography and single photon emission computed tomography. Abnormality of the caudate, thalamus, middle frontal and temporal gyri was common to all parkinsonian disorders. Localizations of commonly affected brain regions in individual disorders aligned with current diagnostic imaging markers, localizing the midbrain in PSP, putamen in MSA-parkinsonian variant and brainstem in MSA-cerebellar variant. Regions of the basal ganglia and precuneus were most commonly affected in PD, while CBS was characterized by caudate abnormality. To our knowledge, this is the largest meta-analysis of neuroimaging studies in parkinsonian disorders. Findings support the notion that parkinsonism may share a common neural substrate, independent of the underlying disease process, while also highlighting characteristic patterns of brain abnormality in each disorder.
Arthritis and antinuclear antibodies (ANA) with inherited deficiency of the sixth component of complement (C6).
Authors: E Reinitz, M Lawrence, B Diamond, H Keiser, C Alper
Journal: Annals of the Rheumatic Diseases (1986)

We report here the case of a woman with joint pains found to have antinuclear antibodies and undetectable serum haemolytic complement. Investigation of her and her family members showed an inherited deficiency of C6.
Elucidating the Autoimmune and Antitumor Effector Mechanisms of a Treatment Based on Cytotoxic T Lymphocyte Antigen-4 Blockade in Combination with a B16 Melanoma Vaccine
Authors: Andrea van Elsas, Roger P.M. Sutmuller, Arthur A. Hurwitz, Jennifer Ziskin, Jennifer Villasenor, Jan-Paul Medema, Willem W. Overwijk, Nicholas P. Restifo, Cornelis J.M. Melief, Rienk Offringa, James P. Allison
Journal: The Journal of Experimental Medicine (2001)

We have previously shown that small B16 melanomas can be successfully treated using a combination of anti-cytotoxic T lymphocyte antigen (CTLA)-4 monoclonal antibody with a granulocyte/macrophage colony-stimulating factor (GM-CSF) producing irradiated tumor cell vaccine. Regression of tumors results in long-lasting immunity and is frequently accompanied by autoimmune depigmentation. Here we examine the cellular and molecular mechanisms of this combined treatment. Histological examination of depigmented lesions revealed infiltration of polymorphonuclear cells and deposition of antibody. The combination therapy also induced tumor rejection and skin depigmentation in B cell-deficient and in CD4(+) T cell-depleted mice. Both effects of the treatment absolutely required CD8(+) T cells. Analysis of the response in successfully treated mice revealed elevated levels of CD8(+) T cells specific for a nonameric peptide consisting of residues 180-188 of the melanocyte differentiation antigen tyrosinase-related protein (TRP)2. There was no evidence of reactivity to the melanocyte antigens gp100, tyrosinase, Mart1/MelanA, or TRP1. Fas-FasL interactions and perforin played a role in mounting the effector response, whereas the tumor necrosis factor pathway was not required. The cellular requirements for tumor rejection in this therapeutic setting were strikingly different from those in a prophylactic setting. In particular, if mice received a prophylactic vaccine consisting of anti-CTLA-4 and B16-GM-CSF before tumor challenge, full protection was obtained even in the absence of CD8(+) T cells. Our data demonstrate that therapeutic autoreactive CD8(+) T cell responses can effectively be generated in tumor-bearing mice and stresses the value of studying tumor immunity in a therapeutic rather than a prophylactic setting.