tbuckley/cabot-search huggingface dataset:
Comparison of polymerase chain reaction amplification of two mycobacterial DNA sequences, IS6110 and the 65kDa antigen gene, in the diagnosis of tuberculosis.
Authors: D A Walker, I K Taylor, D M Mitchell, R J Shaw
Journal: Thorax (1992)

BACKGROUND: Knowledge of the sequences of mycobacterial genes and the availability of DNA amplification techniques have raised the possibility that identification of mycobacterial DNA may offer a rapid and specific diagnostic test for tuberculosis. The correlation between the presence of Mycobacterium tuberculosis DNA and clinical tuberculosis, however, is not known. This study compared the results of polymerase chain reaction amplification of two M tuberculosis DNA sequences, IS6110 and the gene encoding the 65kDa heat shock protein (65kDa Ag), from sputum, bronchoscopy washings, and bronchoalveolar lavage fluid and related these findings to the presence of active and past tuberculosis. METHODS: Highly specific primers were used for amplification of IS6110 and 65kDa Ag DNA. Analysis was performed on one or more samples from 87 patients. RESULTS: IS6110 DNA was identified in samples from all six patients with active tuberculosis, from 15 to 18 patients with past tuberculosis, from five of nine contacts of patients with tuberculosis, and from nine of 54 patients with lung disease unrelated to tuberculosis. The 65kDa Ag DNA was identified in samples from all patients with active and past tuberculosis, from contacts of patients with tuberculosis, and from 14 of 42 patients with non-tuberculous lung diseases. CONCLUSION: These data suggest that the presence of IS6110 DNA correlates more closely with a tuberculosis related diagnosis than that of 65kDa Ag DNA and that both DNAs are found in most subjects with past tuberculosis or contacts of patients with tuberculosis. This may limit the clinical usefulness of these tests.
Three-Dimensional Window Analysis for Detecting Positive Selection at Structural Regions of Proteins
Authors: Yoshiyuki Suzuki
Journal: Molecular Biology and Evolution (2004)

Detection of natural selection operating at the amino acid sequence level is important in the study of molecular evolution. Single-site analysis and one-dimensional window analysis can be used to detect selection when the biological functions of amino acid sites are unknown. Single-site analysis is useful when selection operates more or less constantly over evolutionary time, but less so when selection operates temporarily. One-dimensional window analysis is more sensitive than single-site analysis when the functions of amino acid sites in close proximity in the linear sequence are similar, although this is not always the case. Here I present a three-dimensional window analysis method for detecting selection given the three-dimensional structure of the protein of interest. In the three-dimensional structure, the window is defined as the sphere centered on the α-carbon of an amino acid site. The window size is the radius of the sphere. The sites whose α-carbons are included in the window are grouped for the neutrality test. The window is moved within the three-dimensional structure by sequentially moving the central site along the primary amino acid sequence. To detect positive selection, it may also be useful to group the surface-exposed sites in the window separately. Three-dimensional window analysis appears not only to be more sensitive than single-site analysis and one-dimensional window analysis but also to provide similar specificity for inferring positive selection in the analyses of the hemagglutinin and neuraminidase genes of human influenza A viruses. This method, however, may fail to detect selection when it operates only on a particular site, in which case single-site analysis may be preferred, although a large number of sequences is required.
CD13: Waving the flag for a novel cancer stem cell target
Authors: Bruno Christ, Peggy Stock, Matthias M. Dollinger
Journal: Hepatology (2011)

Cancer stem cells (CSCs) are generally dormant or slowly cycling tumor cells that have the ability to reconstitute tumors. They are thought to be involved in tumor resistance to chemo/radiation therapy and tumor relapse and progression. However, neither their existence nor their identity within many cancers has been well defined. Here, we have demonstrated that CD13 is a marker for semiquiescent CSCs in human liver cancer cell lines and clinical samples and that targeting these cells might provide a way to treat this disease. CD13+ cells predominated in the G0 phase of the cell cycle and typically formed cellular clusters in cancer foci. Following treatment, these cells survived and were enriched along the fibrous capsule where liver cancers usually relapse. Mechanistically, CD13 reduced ROS-induced DNA damage after genotoxic chemo/radiation stress and protected cells from apoptosis. In mouse xenograft models, combination of a CD13 inhibitor and the genotoxic chemotherapeutic fluorouracil (5-FU) drastically reduced tumor volume compared with either agent alone. 5-FU inhibited CD90+ proliferating CSCs, some of which produce CD13+ semiquiescent CSCs, while CD13 inhibition suppressed the self-renewing and tumor-initiating ability of dormant CSCs. Therefore, combining a CD13 inhibitor with a ROS-inducing chemo/radiation therapy may improve the treatment of liver cancer.
Detection of Merkel cell polyomavirus DNA in Merkel cell carcinomas
Authors: E. Varga, M. Kiss, K. Szabó, L. Kemény
Journal: British Journal of Dermatology (2009)

Merkel cell carcinoma (MCC) is a rare, aggressive tumour for which an increasing incidence has been reported. A new human polyomavirus, Merkel cell polyomavirus (MCV), was recently isolated from these tumours by applying digital transcriptome subtraction methodology.To detect the presence or absence of MCV in MCCs and other, randomly selected neoplasms.Nine primary or recurrent MCCs from seven patients were examined; 29 other tumours (squamous cell, basal cell and basosquamous carcinomas and malignant melanomas) were examined for comparative purposes. Viral large T protein (LT1 and LT3), and viral capsid protein (VP1) were detected by primer-directed amplification, using a polymerase chain reaction (PCR)-based method, and the amplified PCR products were analysed by agarose gel electrophoresis and subsequent sequence analysis.The presence of viral T antigen and/or viral capsid DNA sequences was demonstrated in seven of the eight MCC lesions. None of the comparative samples contained MCV DNA.Our findings strongly support the hypothesis that MCV infection may well be specific for MCC, and MCV may play a role in the pathogenesis of MCC.
Bromodomain Inhibition in Diffuse Large B-cell Lymphoma—Giving MYC a Brake
Authors: Anja Mottok, Randy D. Gascoyne
Journal: Clinical Cancer Research (2014)

Bromodomains are conserved protein regions that function as epigenetic readers by recognizing specific histone modifications. The common association of bromodomains with enhancer and super-enhancer regions in diffuse large B-cell lymphoma contributes to its pathogenesis. Bromodomain inhibition reduces tumor growth largely through the disruption of transcriptional networks driven by oncogenic MYC.
Erlotinib as Neoadjuvant Treatment in Endobronchial Ultrasound Confirmed Stage IIIA-N2 Non-Small Cell Lung Cancer (NSCLC) Patients with Epidermal Growth Factor Receptor (EGFR) Mutation (EXON 19 OR 21) (NCT01217619, ESTERN): a Prospective, Single Arm, Phase Ii Clinical Trial
Authors: B. Han, L. Xiong, J. Sun, R. Li, Y. Lou, Y. Zhang, A. Gu, L. Jiang, J. Shi
Journal: Annals of Oncology (2015)
Systematic Review of Combination Drug Therapy for Non-neurogenic Male Lower Urinary Tract Symptoms
Authors: Claudius Füllhase, Christopher Chapple, Jean-Nicolas Cornu, Cosimo De Nunzio, Christian Gratzke, Steven A. Kaplan, Michael Marberger, Francesco Montorsi, Giacomo Novara, Matthias Oelke, Hartmut Porst, Claus Roehrborn, Christian Stief, Kevin T. McVary
Journal: European Urology (2013)
How Success Nearly Wrecked a Residency Experience
Authors: FRANK M. KLINE
Journal: American Journal of Psychiatry (1973)

The number of residents in a second-year program increased almost threefold between 1965 and 1971. Total patient visits increased by almost 100 percent. However, the average number of monthly patient visits per resident decreased, indicating a loss of efficiency. After discussing how the clinic dealt with this problem, the author concludes that increases of this magnitude require the addition of more supervising psychiatrists, changes in administrative style, and adequate clerical assistance and space.
Electrocardiographic Diagnosis of Ventricular Hypertrophy in the Presence of Right Bundle-Branch Block
Authors: RICHARD W. BOOTH, TE-CHUTAN CHOU, RALPH C. SCOTT
Journal: Circulation (1958)

Forty-nine autopsied cases of complete and incomplete right bundle-branch block were studied with correlation of the electrocardiographic and anatomic diagnosis of ventricular hypertrophy. Twenty-six (53 per cent) of the cases showed anatomic evidence of right ventricular hypertrophy. The cases were studied for right ventricular hypertrophy according to the criteria of Barker and Valencia and of Milnor. Milnor's criteria resulted in frequent overdiagnosis while those that met Barker and Valencia's criteria usually but not invariably showed anatomic right ventricular hypertrophy. The electrocardiographic diagnosis of left ventricular hypertrophy was masked by the bundle-branch block in anatomically proved cases.
A Phase II Study of Etanercept (Enbrel), a Tumor Necrosis Factor α Inhibitor in Patients with Metastatic Breast Cancer
Authors: Srinivasan Madhusudan, Martin Foster, Sethupathi R. Muthuramalingam, Jeremy P. Braybrooke, Susan Wilner, Kulwinder Kaur, Cheng Han, Susan Hoare, Frances Balkwill, Denis C. Talbot, Trivadi S. Ganesan, Adrian L. Harris
Journal: Clinical Cancer Research (2004)

Tumor necrosis factor (TNF) alpha is a key player in the tumor microenvironment and is involved in the pathogenesis of breast cancer. Etanercept is a recombinant human soluble p75 TNF receptor that binds to TNF-alpha and renders it biologically unavailable. In the current study, we sought to determine the toxicity, biological activity, and therapeutic efficacy of Etanercept in metastatic breast cancer.We initiated a Phase II, nonrandomized, open-labeled study in patients with progressive metastatic breast cancer refractory to conventional therapy (Phase I toxicity data were available in patients with rheumatoid arthritis). Etanercept was administered subcutaneously at a dose of 25 mg twice weekly until disease progression.Sixteen patients were recruited [median age 53 years (range, 34 to 74)]. A total of 141.6 weeks of therapy was administered (median of 8.1 weeks). Seven patients received > or =12 weeks of therapy. The most common side effects were injection site reactions (6), fatigue (5), loss of appetite (2), nausea (1), headache (1), and dizziness (1). Brief period of disease stabilization was seen in 1 patient lasting for 16.4 weeks. Immunoreactive TNF-alpha was elevated within 24 hours of therapy and persisted until the end of treatment (days 7, 28, 56, and 84). Phytohemagglutinin stimulates the production of interleukin-6 and CCL2 in peripheral blood cells, and the ability of Etanercept to modulate this response was assessed in a cytokine release assay. A consistent decrease in interleukin-6 and CCL2 level was seen compared with pretreatment values in serial blood samples (days 1, 7, 28, 56, and 84).Our study shows the safety and biological activity of Etanercept in breast cancer and provides data to assess pharmacodynamic endpoints of different schedules of Etanercept and combinations with chemotherapy or other biological therapies.
IL-22, but Not IL-17, Dominant Environment in Cutaneous T-cell Lymphoma
Authors: Tomomitsu Miyagaki, Makoto Sugaya, Hiraku Suga, Masahiro Kamata, Hanako Ohmatsu, Hideki Fujita, Yoshihide Asano, Yayoi Tada, Takafumi Kadono, Shinichi Sato
Journal: Clinical Cancer Research (2011)

Both patients with cutaneous T-cell lymphoma (CTCL) and those with atopic dermatitis (AD) have pruritus, T(H)2-biased T cells, and a tendency to have bacterial infections, suggesting a common pathologic basis for these two diseases. Recently, interleukin (IL)-22-producing T cells were reported in skin of patients with AD. In this study, we investigated expression levels of T(H)22- and T(H)17-related molecules in lesional skin and sera isolated from patients with CTCL.Skin biopsies and sera were collected from patients with CTCL or psoriasis and from healthy volunteers. Protein and mRNA expression levels of IL-22, IL-17A, IL-17F, IL-23p19, IL-10, IL-4, CCL20, CCR6, IL-8, and IL-20 were examined in lesional tissue and a subset of these molecules in sera. Phosphorylation of STAT3 was also assessed in lesional skin of CTCL and psoriasis by immunohistochemistry.IL-22, IL-10, IL-4, CCL20, and CCR6 mRNA and protein levels, but not IL-17A, IL-17F, IL-23p19, IL-8, or IL-20, were significantly elevated in lesional skin of CTCL. Phosphorylation of STAT3 was detected in epidermis of CTCL skin. Moreover, serum IL-22, IL-10, and CCL20 levels were increased in CTCL and correlated with disease severity.Our results suggest that IL-22 is important in establishing the tumor microenvironment for CTCL. Enhanced expression of CCL20 may explain epidermal hyperplasia and migration of CCR6(+) cells, such as Langerhans cells, into lesional skin. Relatively low expression of IL-17 may explain the lack of neutrophils in lesions of CTCL, which correlates with bacterial infections that commonly occur in skin affected by CTCL.
Interleukin 2 Signaling Is Required for CD4+ Regulatory T Cell Function
Authors: Gláucia C. Furtado, Maria A. Curotto de Lafaille, Nino Kutchukhidze, Juan J. Lafaille
Journal: The Journal of Experimental Medicine (2002)

Mice deficient in interleukin (IL)-2 production or the IL-2 receptor α or β chains develop a lethal autoimmune syndrome. CD4+ regulatory T cells have been shown to prevent autoimmune diseases, allograft rejection, and to down-regulate antibody responses against foreign antigens. To assess the role of IL-2 in the generation and function of regulatory T cells, we transferred CD4+ T cells from mice genetically deficient in IL-2 or IL-2Rα (CD25) expression. A small number of splenic or thymic CD4+ T cells from IL-2 knockout mice can protect mice from spontaneous experimental autoimmune encephalomyelitis (EAE). In contrast, splenic or thymic CD4+ T cells from CD25 knockout donor mice conferred little or no protection. We conclude that T cells with regulatory potential can develop, undergo thymic selection, and migrate to the peripheral lymphoid organs in the absence of IL-2, and do not protect from disease by means of IL-2 secretion. However, IL-2 signaling in regulatory T cells is essential for their protective function. Altogether, our results favor a model whereby IL-2 induces regulatory T cell activity.
THE WELL-BEING CLINIC: A STUDY OF THE EFFECTIVENESS OF AN ATTEMPT TO PROVIDE ROUTINE MENTAL HEALTH CHECK-UPS FOR COMMUNITY GROUPS
Authors: A. W. MACLEOD, B. SILVERMAN, PHYLLIS POLAND
Journal: American Journal of Psychiatry (1957)

The existence of a Well-Being Clinic should in itself be an encouragement to people to seek help in emotional problems. The positive health orientation of the clinic lessens the likelihood of those exploring the state of their mental health being labelled "neurotic." It should help relieve chronic and often unnecessary concern about mental health derived from the public's misinterpretation of well-intentioned mental health propaganda. It should help in the early detection of mental illnesses and social maladjustment thus making early treatment possible. And it should make useful contributions to the field of psychiatric research by assisting in the assessment of the effectiveness of existing treatment resources and perhaps by identifying as yet unrecognized disturbed human relationships. On the negative side it can be said that the clinic may bring to light many cases for whom there is at present no therapeutic resource, and that it may miss many cases of early illness. The degree of effectiveness of the initial screening interview may roughly parallel that obtained in mass radiography of the chest in the field of preventive public health. Yet compared with a community in which a Well-Being Clinic does not exist, it can be argued that Montreal has set in motion a promising venture. The idea of the Well-Being Clinic has been favorably received in Montreal. Professional and industrial organizations have shown an interest in setting up further clinics adapted to their particular needs. Outlying communities have expressed similar interest. The clinics in Montreal have remained financially self-supporting. And the 2 group programs to which they were attached had over the past year a paying enrolment of 200 persons. The clinics, therefore, have not been a costly experiment. Remembering that in the final analyses it is the well people of the community who must carry the burden of the ill, and this is by no means only a financial burden, it is of paramount importance that experimentation should go forward in the direction of keeping the healthy as healthy as possible.
The heterogeneity of chronic obstructive pulmonary disease
Authors: J A WEDZICHA
Journal: Thorax (2000)

The study describes a detailed evaluation of 110 patients who presented to primary care with a diagnosis of an acute exacerbation of COPD and who were later, after two months when clinically stable, investigated with full lung function and, most interestingly, with CT scanning. The findings of this paper suggest some novel characteristics of this important disease and challenge some of the accepted definitions of COPD. The results showed that 30% of the patients with a diagnosis of COPD had a normal FEV1 (>80% predicted) when stable, though nearly half of these patients had a reduced FEV1/FVC ratio which suggests that airflow obstruction was indeed present, though the criteria in the BTS COPD guidelines were not fulfilled. Thus, future guidelines for the management of COPD may have to revise their definitions to encompass patients with early COPD, as in this paper. This study also emphasises the importance of measuring the vital capacity in these patients. Only 5% of the cohort showed a significant bronchodilator response, suggesting that a diagnosis of asthma was not a prominent feature in this study. However, a limitation of the study is that patients were only included if they had an exacerbation, and some COPD patients with progressive airflow obstruction may have only infrequent exacerbations and would not have been part of this particular cohort. 1
MAT1-Modulated Cyclin-Dependent Kinase-Activating Kinase Activity Cross-Regulates Neuroblastoma Cell G1 Arrest and Neurite Outgrowth
Authors: Shineng Zhang, Qiaojun He, Hui Peng, Nicole Tedeschi-Blok, Timothy J. Triche, Lingtao Wu
Journal: Cancer Research (2004)

Abstract Cyclin-dependent kinase-activating kinase (CAK) regulates cell cycle G1 exit, where cells commonly commit either to proliferate or to differentiate. CAK activity in G1 regulation is determined by its assembly factor and targeting subunit, ménage à trois 1 (MAT1). The precise mechanism of how proliferation/differentiation transition is induced from cancer cell G1 arrest remains unknown. We present evidence that in neuroblastoma CHP126 cells, CAK interacts with and phosphorylates retinoblastoma tumor suppressor protein (pRb) and retinoid X receptor α (RXRα). Retinoic acid (RA)-induced neuroblastoma cell proliferation/differentiation transition is associated with decreased CAK activity, as evidenced by a switch from CAK hyperphosphorylation of pRb and RXRα to hypophosphorylation of pRb and RXRα. Manipulation of MAT1 abundance shows that MAT1 reduction mimics RA-induced hypophosphorylation of pRb/RXRα, proliferation inhibition, and neurite outgrowth, whereas MAT1 overexpression resists these RA actions. Thus, these findings reveal an important mechanism by which MAT1-modulated CAK activity is crucial in the switch from proliferation to differentiation in neuroblastoma cells.
Ancient Origin and Recent Innovations of RNA Polymerase IV and V
Authors: Yi Huang, Timmy Kendall, Evan S. Forsythe, Ana Dorantes-Acosta, Shaofang Li, Juan Caballero-Pérez, Xuemei Chen, Mario Arteaga-Vázquez, Mark A. Beilstein, Rebecca A. Mosher
Journal: Molecular Biology and Evolution (2015)

Small RNA-mediated chromatin modification is a conserved feature of eukaryotes. In flowering plants, the short interfering (si)RNAs that direct transcriptional silencing are abundant and subfunctionalization has led to specialized machinery responsible for synthesis and action of these small RNAs. In particular, plants possess polymerase (Pol) IV and Pol V, multi-subunit homologs of the canonical DNA-dependent RNA Pol II, as well as specialized members of the RNA-dependent RNA Polymerase (RDR), Dicer-like (DCL), and Argonaute (AGO) families. Together these enzymes are required for production and activity of Pol IV-dependent (p4-)siRNAs, which trigger RNA-directed DNA methylation (RdDM) at homologous sequences. p4-siRNAs accumulate highly in developing endosperm, a specialized tissue found only in flowering plants, and are rare in nonflowering plants, suggesting that the evolution of flowers might coincide with the emergence of specialized RdDM machinery. Through comprehensive identification of RdDM genes from species representing the breadth of the land plant phylogeny, we describe the ancient origin of Pol IV and Pol V, suggesting that a nearly complete and functional RdDM pathway could have existed in the earliest land plants. We also uncover innovations in these enzymes that are coincident with the emergence of seed plants and flowering plants, and recent duplications that might indicate additional subfunctionalization. Phylogenetic analysis reveals rapid evolution of Pol IV and Pol V subunits relative to their Pol II counterparts and suggests that duplicates were retained and subfunctionalized through Escape from Adaptive Conflict. Evolution within the carboxy-terminal domain of the Pol V largest subunit is particularly striking, where illegitimate recombination facilitated extreme sequence divergence.
Biochemical Markers of Central Nervous System Tumors Measured in Cerebrospinal Fluid and Their Potential Use in Diagnosis and Patient Management: A Review&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J Seidenfeld, L J Marton
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Biochemical Markers of Central Nervous System Tumors Measured in Cerebrospinal Fluid and Their Potential Use in Diagnosis and Patient Management: A Review Get access Jerome Seidenfeld, Jerome Seidenfeld Search for other works by this author on: Oxford Academic PubMed Google Scholar Laurence J. Marton Laurence J. Marton 6 6Address reprint requests to Dr. L. J. Marton, Brain Tumor Research Center. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 63, Issue 4, October 1979, Pages 919–931, https://doi.org/10.1093/jnci/63.4.919 Published: 01 October 1979 Article history Received: 05 October 1978 Accepted: 12 March 1979 Published: 01 October 1979