tbuckley/cabot-search huggingface dataset:
Effect of an MMP-9/MMP-12 inhibitor on smoke-induced emphysema and airway remodelling in guinea pigs
Authors: A. Churg, R. Wang, X. Wang, P.-O. Onnervik, K. Thim, J. L Wright
Journal: Thorax (2007)

<h3>Abstract</h3> Urinary tract infections (UTI) affect half of all women at least once during their lifetime. The rise in extended-spectrum beta-lactamase-producing strains and potential for carbapenem resistance within uropathogenic <i>Escherichia coli</i> (UPEC), the most common causative agent of UTIs, creates an urgent need for vaccine development. Intranasal immunization of mice with UPEC outer membrane iron receptors, FyuA, Hma, IreA, or IutA, conjugated to cholera toxin, provides protection in the bladder or kidneys when challenged with UPEC CFT073 or 536. Based on these data, we sought to optimize the vaccination route (intramuscular, intranasal, or subcutaneous) in combination with adjuvants suitable for human use including alum, monophosphoryl lipid A (MPLA), unmethylated CpG synthetic oligodeoxynucleotides (CpG), polyinosinic:polycytodylic acid (polyIC), and mutated heat-labile <i>E. coli</i> enterotoxin (dmLT). Mice intranasally vaccinated with dmLT-IutA or dmLT-Hma displayed a significant reduction in bladder colonization (86-fold and 32-fold, respectively) with 40–42% of mice having no detectable colony forming units (CFU). Intranasal vaccination of mice with CpG-IutA and polyIC-IutA significantly reduced kidney colonization (131-fold) and urine CFU (22-fold), respectively. dmLT generated the most consistently robust antibody response in intranasally immunized mice, while MPLA and alum produced greater concentrations of antigen-specific serum IgG with intramuscular immunization. Based on these results, we conclude that intranasal administration of Hma or IutA formulated with dmLT adjuvant provides the greatest protection from UPEC UTI. This study advances our progress toward a vaccine against uncomplicated UTI, which will significantly improve the quality of life for women burdened by recurrent UTI and enable better antibiotic stewardship. <h3>Importance</h3> Urinary tract infections (UTI) are among the most common bacterial infection in humans, affecting half of all women at least once during their lifetimes. The rise in antibiotic resistance and health care costs emphasizes the need to develop a vaccine against the most common UTI pathogen, <i>Escherichia coli.</i> Vaccinating mice intranasally with a detoxified heat-labile enterotoxin and two surface exposed receptors, Hma or IutA, significantly reduced bacterial burden in the bladder. This work highlights progress in the development of a UTI vaccine formulated with adjuvants suitable for human use and antigens that encode outer membrane iron receptors required for infection in the iron-limited urinary tract.
Repeatability of methacholine challenge in asthmatic children measured by change in transcutaneous oxygen tension.
Authors: S B Phagoo, N M Wilson, M Silverman
Journal: Thorax (1992)

BACKGROUND: The airway response to bronchial provocation may be evaluated by monitoring the fall in transcutaneous oxygen tension (PtcO2) but the repeatability of this method has not been rigorously assessed. METHODS: To determine the repeatability of this indirect method of assessment, bronchial challenge was performed with methacholine in nine children with stable asthma (age range 6-12 years) and was repeated 24 hours later. The response was determined by the fall both in forced expiratory volume in one second (FEV1) and in PtcO2. A modified tidal inhalation protocol was used in which quadrupling concentrations of methacholine were given, thereby reducing the time taken for the full challenge by almost half. The concentrations of methacholine that provoked a 20% decrease in FEV1 (PC20FEV1) and 15% and 10% falls in PtcO2 (PC15PtcO2, PC10PtcO2) were calculated. RESULTS: Repeatability measures, assessed as the 95% range for a single determination, were +/- 0.96 and +/- 1.12 doubling concentration differences respectively for PC15PtcO2 and PC10PtcO2 and +/- 0.80 for PC20FEV1. CONCLUSION: This challenge method using quadrupling concentrations and an indirect assessment of the response by PtcO2 was sufficiently repeatable for clinical use and compared favourably with repeated challenge assessed by FEV1. The PtcO2 method is simple and effort independent, and should prove particularly useful for measuring bronchial reactivity in young children.
Functional Sympatholysis During Muscular Activity
Authors: John P. Remensnyder, Jere H. Mitchell, Stanley J. Sarnoff
Journal: Circulation Research (1962)

The effects of both direct and reflexly induced increases in sympathetic activity on the blood flow to an extremity at rest and during muscular activity have been studied. When the O 2 uptake of an extremity is increased during muscular activity, its vascular resistance falls sharply with a small increase in O 2 uptake and thereafter declines only slightly. The responsiveness of a vascular bed to adrenergic stimulation diminishes sharply with a small increase in O 2 uptake and thereafter diminishes only slightly. The role of the carotid sinus as a sense organ which helps to regulate blood flow to the various tissues of the organism in accordance with their varying metabolic requirements rather than one which acts only as a receptor that helps to safeguard flow to the vital organs has been discussed.
Accuracy of CT Colonography for Detection of Large Adenomas and Cancers
Authors: C. Daniel Johnson, Mei-Hsiu Chen, Alicia Y. Toledano, Jay P. Heiken, Abraham Dachman, Mark D. Kuo, Christine O. Menias, Betina Siewert, Jugesh I. Cheema, Richard G. Obregon, Jeff L. Fidler, Peter Zimmerman, Karen M. Horton, Kevin Coakley, Revathy B. Iyer, Amy K. Hara, Robert A. Halvorsen, Giovanna Casola, Judy Yee, Benjamin A. Herman, Lawrence J. Burgart, Paul J. Limburg
Journal: New England Journal of Medicine (2008)

Computed tomographic (CT) colonography is a noninvasive option in screening for colorectal cancer. However, its accuracy as a screening tool in asymptomatic adults has not been well defined.
54 COMPLETELY INDIVIDUALIZED TREATMENT DURATIONS (24, 30, 36, 42, 48, 60 OR 72 WEEKS) WITH PEGINTERFERON-ALFA-2B AND RIBAVIRIN IN HCV GENOTYPE 1-INFECTED PATIENTS (INDIV-2 STUDY)
Authors: C. Sarrazin, S. Schwendy, B. Möller, N. Dikopoulos, P. Buggisch, J. Encke, G. Teuber, T. Goeser, R. Thimme, H. Klinker, W.O. Boecher, E. Schulte-Frohlinde, R. Prinzing, T. Berg, S. Zeuzem
Journal: Journal of Hepatology (2010)
Dietary Therapy in Type II Diabetes Mellitus: Correction-Reply
Authors: Mark R. Burge
Journal: JAMA (1995)

<h3>In Reply.</h3> —Thank you for pointing out an inaccuracy in our Questions and Answers response. The proportions of the different kinds of dietary fats reported in the second paragraph of the response are erroneous. Specifically, saturated fats should be avoided in favor of polyunsaturated and monounsaturated fats (these two words are transposed in the sentence in question). Saturated fats should ideally not constitute more than 6% to 8% of daily energy intake, while polyunsaturated fats should be limited to less than 10% of daily energy intake. The remainder of fat in the diabetic diet should thus consist of monounsaturated fats, with total daily fat intake not to exceed 30% of daily energy intake. We regret this error and appreciate the opportunity to clarify our answer.
Ad.Egr-TNF and Local Ionizing Radiation Suppress Metastases by Interferon-β-Dependent Activation of Antigen-specific CD8+ T Cells
Authors: Yuru Meng, Helena J Mauceri, Nikolai N Khodarev, Thomas E Darga, Sean P Pitroda, Michael A Beckett, Donald W Kufe, Ralph R Weichselbaum
Journal: Molecular Therapy (2010)

Ad.Egr-TNF is a radioinducible adenovector currently in phase 3 trials for inoperable pancreatic cancer. The combination of Ad.Egr-TNF and ionizing radiation (IR) contributes to local tumor control through the production of tumor necrosis factor-α (TNFα) in the tumor microenvironment. Moreover, clinical and preclinical studies with Ad.Egr-TNF/IR have suggested that this local approach suppresses the growth of distant metastatic disease; however, the mechanisms responsible for this effect remain unclear. These studies have been performed in wild-type (WT) and TNFR1,2−/− mice to assess the role of TNFα-induced signaling in the suppression of draining lymph node (DLN) metastases. The results demonstrate that production of TNFα in the tumor microenvironment induces expression of interferon (IFNβ). In turn, IFNβ stimulates the production of chemokines that recruit CD8+ T cells to the tumor. The results further demonstrate that activation of tumor antigen–specific CD8+ CTLs contributes to local antitumor activity and suppression of DLN metastases. These findings support a model in which treatment of tumors with Ad.Egr-TNF and IR is mediated by local and distant immune-mediated antitumor effects that suppress the development of metastases. Ad.Egr-TNF is a radioinducible adenovector currently in phase 3 trials for inoperable pancreatic cancer. The combination of Ad.Egr-TNF and ionizing radiation (IR) contributes to local tumor control through the production of tumor necrosis factor-α (TNFα) in the tumor microenvironment. Moreover, clinical and preclinical studies with Ad.Egr-TNF/IR have suggested that this local approach suppresses the growth of distant metastatic disease; however, the mechanisms responsible for this effect remain unclear. These studies have been performed in wild-type (WT) and TNFR1,2−/− mice to assess the role of TNFα-induced signaling in the suppression of draining lymph node (DLN) metastases. The results demonstrate that production of TNFα in the tumor microenvironment induces expression of interferon (IFNβ). In turn, IFNβ stimulates the production of chemokines that recruit CD8+ T cells to the tumor. The results further demonstrate that activation of tumor antigen–specific CD8+ CTLs contributes to local antitumor activity and suppression of DLN metastases. These findings support a model in which treatment of tumors with Ad.Egr-TNF and IR is mediated by local and distant immune-mediated antitumor effects that suppress the development of metastases.
PNEUMOCOCCAL SEROTYPES IN WEST AFRICA
Authors: B.M. Greenwood, M. Hassan-King, J.T. Macfarlane, P.J. Tugwell, F. Denis, S. M'Boup, M. Cadoz, G. Onyemelukwe, H.R. Tubbs, H.C. Whittle, J.P. Chiron, R. Triau, I. Diop Mar
Journal: The Lancet (1980)
Role of Ox40 Signals in Coordinating Cd4 T Cell Selection, Migration, and Cytokine Differentiation in T Helper (Th)1 and Th2 Cells
Authors: Peter Lane
Journal: The Journal of Experimental Medicine (2000)

Our survival depends on our ability to clonally expand rare CD4 lymphocytes and instruct them to help effector cells. Two very different types of CD4 T cell response are required for protective immunity. Immunity to intracellular infections like tuberculosis is dependent on priming and expanding
Abstract PR10: Modulation of chromatin structure and transcription by the SWI/SNF complex in acute lymphoblastic leukemia
Authors: Jennifer Wu, Luca Pinello, Elinor Yissachar, Guo-Cheng Yuan, Charles Roberts
Journal: Cancer Research (2013)

Abstract SWI/SNF chromatin remodelers act as tumor suppressors in a wide variety of tissue types and cancers. Recent reports describe that as many as 20% of human cancers harbor mutations in one or more subunits of this multi-protein complex. Intriguingly, mutations in the SWI/SNF complex are rarely found in leukemias. However, it has long been understood that SWI/SNF is a key component of glucocorticoid-mediated transcription. Diminished expression of SWI/SNF subunits has also been linked to altered sensitivity to glucocorticoid-induced cell death in acute lymphoblastic leukemias (ALL). Glucocorticoid-induced cell death is a critical component of successful ALL therapy. We therefore use the glucocorticoid-mediated transcriptional program in a human ALL cell line to interrogate the genome-wide chromatin changes and contributions to transcription mediated by an intact SWI/SNF complex. We begin by elucidating the dynamic relationships between glucocorticoid receptor binding to chromatin and recruitment of SWI/SNF using ChIP-Seq. We further relate these glucocorticoid-inducible binding events to changes in position of modified histones, changes in chromatin accessibility by DNase-seq, and changes in gene expression. By better understanding the mechanisms by which SWI/SNF modifies the chromatin landscape within a specific transcriptional program, we will facilitate additional studies of how disruption of the SWI/SNF complex affects ALL responses to steroid therapy. Furthermore, we will contribute to future studies of how mutations in the SWI/SNF complex functionally affect chromatin structure and contribute to oncogenesis. This abstract is also presented as Poster B07. Citation Format: Jennifer Wu, Luca Pinello, Elinor Yissachar, Guo-Cheng Yuan, Charles Roberts. Modulation of chromatin structure and transcription by the SWI/SNF complex in acute lymphoblastic leukemia. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr PR10.
Skin Protection: Biocompatible Films with Tailored Spectral Response for Prevention of DNA Damage in Skin Cells (Adv. Healthcare Mater. 13/2015)
Authors: Rebeca Núñez‐Lozano, Belén Pimentel, José R. Castro‐Smirnov, Mauricio E. Calvo, Hernán Míguez, Guillermo de la Cueva‐Méndez
Journal: Advanced Healthcare Materials (2015)

On page 1944, H. Míguez, G. de la Cueva-Méndez, and co-workers present flexible biocompatible films made of a sequence of nanostructured layers, which provide an alternative absorption-free approach to protect human epithelial cells against the noxious effects of ultraviolet radiation. Photo-induced damage of DNA is identified by the presence of cyclobutene pyrimidine dimers (green stained nuclei), which are absent in unharmed cells (blue stained nuclei).
Differential Effect of Unilateral and Bilateral ECT
Authors: J. J. FLEMINGER, D. J. DE L.HORNE, N. P.V. NAIR, P. N. NOTT
Journal: American Journal of Psychiatry (1970)

A double-blind clinical trial compared the effects on three patient groups of bilateral ECT and unilateral ECT to the dominant and nondominant hemispheres. After six ECTs there was no significant difference among the three groups in depression relief. However, unilateral ECT to the nondominant hemisphere reduced the chance of memory disturbance and offered the best chance of quick recovery with few side effects. The authors conclude that it is the treatment of choice when ECT is given for depression.
Postinfantile giant-cell transformation in hepatitis
Authors: Kenneth Devaney, Zachary D. Goodman, Kamal G. Ishak
Journal: Hepatology (1992)

Giant-cell hepatitis is a frequent pattern of liver injury in the neonate, but it is rare after infancy. Such cases have been attributed to autoimmune disease, to non-A, non-B hepatitis and, most recently, to paramyxovirus infection. To better define the entity of postinfantile (syncytial) giant-cell hepatitis, we reviewed 24 biopsy specimens from 20 patients with this finding, either alone or in combination with other diagnoses. The number of multinucleated giant cells varied greatly from one specimen to another. Varying degrees of portal inflammation appeared in all but one of the patients, and all had hepatitislike acinar inflammation associated with hepatocellular injury. Fibrosis was a common finding, varying from mild periportal fibrosis to established cirrhosis (33%). The changes were interpreted as acute giant-cell hepatitis in 25%, as CAH in 42% and as active cirrhosis in the remainder. The patients ranged in age from 2 to 80 yr, with a mean of 35 yr and a male/female ratio of approximately 1:1. The signs and symptoms of liver disease were present for more than 1 mo in most patients. A positive antinuclear antibody titer was found in seven of the patients. Three patients had a direct Coombs reaction and anemia. Overall, evidence of autoimmune disease was found in 40% of the patients. One patient had non-Hodgkin's lymphoma involving the liver. Only one patient had a history of blood transfusion or risk factors for hepatitis C. No patient underwent serological study for paramyxovirus antibodies. Liver tissue from one patient was examined ultrastructurally, but no viral particles could be identified.(ABSTRACT TRUNCATED AT 250 WORDS)
Prevalence and Trends of a Metabolic Syndrome Phenotype Among U.S. Adolescents, 1999–2000
Authors: Glen E. Duncan, Sierra M. Li, Xiao-Hua Zhou
Journal: Diabetes Care (2004)

OBJECTIVE—To determine the prevalence of a metabolic syndrome phenotype among U.S. adolescents using the most recent national data and to examine trends in metabolic syndrome prevalence. RESEARCH DESIGN AND METHODS—Analysis of data on 991 adolescents (aged 12–19 years) who had fasted for at least 6 h, from the National Health and Nutrition Examination Survey (NHANES 1999–2000). The metabolic syndrome was determined using the National Cholesterol Education Program (Adult Treatment Panel III) definition modified for age. RESULTS—The overall prevalence of a metabolic syndrome phenotype among U.S. adolescents increased from 4.2% in NHANES III (1988–1992) to 6.4% in NHANES 1999–2000 (P &amp;lt; 0.001). The syndrome was more prevalent (P &amp;lt; 0.01) in male than female adolescents (9.1 vs. 3.7%) and was found in 32.1% of overweight adolescents (BMI ≥95th percentile for age and sex), compared with 7.1% of adolescents at risk for overweight (BMI between 85th and 95th percentiles) (P &amp;lt; 0.001). Based on population-weighted estimates, &amp;gt;2 million U.S. adolescents currently have a metabolic syndrome phenotype. CONCLUSIONS—The prevalence of a metabolic syndrome phenotype has increased significantly over the past decade among U.S. adolescents and is particularly prevalent (&amp;gt;30%) in overweight adolescents. These findings have important implications for public health because of the well-known health risks associated with the metabolic syndrome in adults.
Strong and Weak Male Mutation Bias at Different Sites in the Primate Genomes: Insights from the Human-Chimpanzee Comparison
Authors: James Taylor, Svitlana Tyekucheva, Michael Zody, Francesca Chiaromonte, Kateryna D Makova
Journal: Molecular Biology and Evolution (2005)

Male mutation bias is a higher mutation rate in males than in females thought to result from the greater number of germ line cell divisions in males. If errors in DNA replication cause most mutations, then the magnitude of male mutation bias, measured as the male-to-female mutation rate ratio (alpha), should reflect the relative excess of male versus female germ line cell divisions. Evolutionary rates averaged among all sites in a sequence and compared between mammalian sex chromosomes were shown to be indeed higher in males than in females. However, it is presently unknown whether individual classes of substitutions exhibit such bias. To address this issue, we investigated male mutation bias separately at non-CpG and CpG sites using human-chimpanzee whole-genome alignments. We observed strong male mutation bias at non-CpG sites: alpha in the X-autosome comparison was approximately 6-7, which was similar to the male-to-female ratio in the number of germ line cell divisions. In contrast, mutations at CpG sites exhibited weak male mutation bias: alpha in the X-autosome comparison was only approximately 2-3. This is consistent with the methylation-induced and replication-independent mechanism of CpG transitions, which constitute the majority of mutations at CpG sites. Interestingly, our study also indicated weak male mutation bias for transversions at CpG sites, implying a spontaneous mechanism largely not associated with replication. Male mutation bias was equally strong at CpG and non-CpG sites located within unmethylated "CpG islands," suggesting the replication-dependent origin of these mutations. Thus, we found that the strength of male mutation bias is nonuniform in the primate genomes. Importantly, we discovered that male mutation bias depends on the proportion of CpG sites in the loci compared. This might explain the differences in the magnitude of primate male mutation bias observed among studies.
The interferon‐regulated gene signature is elevated in subacute cutaneous lupus erythematosus and discoid lupus erythematosus and correlates with the cutaneous lupus area and severity index score
Authors: I. Braunstein, R. Klein, J. Okawa, V.P. Werth
Journal: British Journal of Dermatology (2012)

There is increased expression of type I interferon (IFN)-regulated proteins in the blood and target tissues of patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). Patients with SLE have increased IFN-regulated gene expression pointing towards a possible underlying genetic defect.To determine expression levels of five type I IFN-regulated genes that are highly expressed in SLE in the peripheral blood of patients with CLE and to correlate the expression levels with cutaneous disease activity.Peripheral blood was obtained from 10 healthy controls and 30 patients with CLE, including eight with concomitant SLE. Total RNA was extracted and reverse transcribed into complementary DNA. Gene expression levels were measured by real-time polymerase chain reaction. Gene expression was normalized to GAPDH, standardized to healthy controls and then summed to calculate an IFN score for each patient. Disease activity was assessed with the Cutaneous Lupus Area and Severity Index (CLASI).Patients with subacute CLE (SCLE) and discoid lupus erythematosus (DLE) had elevated IFN scores compared with healthy controls regardless of concomitant SLE (P < 0·01 with SLE and P < 0·05 without SLE). There was no difference between patients with tumid lupus erythematosus (TLE) and healthy controls. The IFN score correlated with CLASI scores (Spearman's rho = 0·55, P = 0·0017).Patients with SCLE and DLE have an IFN signature, as seen in SLE. The level of gene expression correlates with cutaneous disease activity. These findings support a shared pathogenesis between SLE and some subtypes of CLE.
Insulin Gene Mutations as Cause of Diabetes in Children Negative for Five Type 1 Diabetes Autoantibodies
Authors: Riccardo Bonfanti, Carlo Colombo, Valentina Nocerino, Ornella Massa, Vito Lampasona, Dario Iafusco, Matteo Viscardi, Giuseppe Chiumello, Franco Meschi, Fabrizio Barbetti
Journal: Diabetes Care (2008)

Heterozygous, gain-of-function mutations of the insulin gene can cause permanent diabetes with onset ranging from the neonatal period through adulthood. The aim of our study was to screen for the insulin gene in patients who had been clinically classified as type 1 diabetic but who tested negative for type 1 diabetes autoantibodies.We reviewed the clinical records of 326 patients with the diagnosis of type 1 diabetes and identified seven probands who had diabetes in isolation and were negative for five type 1 diabetes autoantibodies. We sequenced the INS gene in these seven patients.In two patients whose diabetes onset had been at 2 years 10 months of age and at 6 years 8 months of age, respectively, we identified the mutation G(B8)S and a novel mutation in the preproinsulin signal peptide (A(Signal23)S).Insulin gene mutations are rare in absolute terms in patients classified as type 1 diabetic (0.6%) but can be identified after a thorough screening of type 1 diabetes autoantibodies.