tbuckley/cabot-search huggingface dataset:
Exhaled nitric oxide during acute changes of airways calibre in asthma
Authors: P Garnier, I Fajac, JF Dessanges, J Dall'Ava-Santucci, A Lockhart, AT Dinh-Xuan
Journal: European Respiratory Journal (1996)

It has been shown that endogenous nitric oxide (NO), measured in exhaled air, is increased in asthmatic subjects and after allergen challenge in sensitized animals. NO is also a paracrine molecule with some, though weak, bronchodilator effects. However, whether the amount of endogenous NO that originates in the lungs can reflect the degree of bronchial tone and airways calibre in asthmatic subjects has not yet been investigated. The aim of this study was, therefore, to determine whether NO production could be modified by acute changes of airways calibre in mild, nonatopic, asthmatic subjects. NO output was measured in the exhaled air of 14 steroid-free asthmatics, 8 steroid-treated asthmatics and 21 control subjects. In seven steroid-free asthmatics, exhaled NO was measured after methacholine challenge, and then after salbutamol-induced bronchial dilatation. Exhaled tidal breathing was collected for 30 s and NO in the exhaled air was measured with a chemiluminescence analyser. Both NO concentration and its output were significantly higher in the steroid-free asthmatic patients (15.6 +/- 1.5 parts per billion (ppb) and 6.3 +/- 0.7 nmol.min-1, respectively) as compared with the control subjects (8.9 +/- 1.0 ppb and 3.5 +/- 0.3 nmol.min-1, respectively; p &lt; 0.001 for both) and with the steroid-treated asthmatic patients (11.3 +/- 3.3 ppb and 3.7 +/- 0.9 nmol.min-1, respectively; p &lt; 0.05 for both). Neither methacholine-induced bronchial obstruction nor salbutamol-induced bronchial dilatation caused a significant change in exhaled NO. We conclude that NO production is higher in steroid-free than in steroid-treated asthmatics and in control subjects. Furthermore, NO production is not affected by acute pharmacologically-induced changes of airways calibre in asthmatic subjects. Our results suggest that NO production is a marker of airways inflammation rather than an endogenous modulator of bronchial tone in asthma.
Clinical, microbiological, and immunological effects of fructo-oligosaccharide in patients with Crohn's disease
Authors: J O Lindsay
Journal: Gut (2005)

<b>Background and aims:</b> The intestinal microbiota play a pivotal role in the inflammation associated with Crohn's disease through their interaction with the mucosal immune system. Some bifidobacteria species are immunoregulatory and induce increased dendritic cell interleukin 10 (IL-10) release in vitro. Fructo-oligosaccharides (FOS) increase faecal and mucosal bifidobacteria in healthy volunteers. The aim of this study was to assess the effect of FOS administration on disease activity, bifidobacteria concentrations, and mucosal dendritic cell function in patients with moderately active Crohn's disease. <b>Patients and methods:</b> Ten patients with active ileocolonic Crohn's disease received 15 g of FOS for three weeks. Disease activity was measured using the Harvey Bradshaw index. Faecal and mucosal bifidobacteria were quantified by fluorescence in situ hybridisation, and mucosal dendritic cell IL-10 and Toll-like receptor (TLR) expression were assessed by flow cytometry of dissociated rectal biopsies. <b>Results:</b> FOS induced a significant reduction in the Harvey Bradshaw index from 9.8 (SD 3.1) to 6.9 (3.4) (p&lt;0.01). There was a significant increase in faecal bifidobacteria concentration from 8.8 (0.9) log<sub>10</sub> to 9.4 (0.9) log<sub>10</sub> cells/g dry faeces (p&lt;0.001). The percentage of IL-10 positive dendritic cells increased from 30 (12)% to 53 (10)% (p = 0.06). Finally, the percentage of dendritic cells expressing TLR2 and TLR4 increased from 1.7 (1.7)% to 36.8 (15.9)% (p = 0.08) and from 3.6 (3.6)% to 75.4 (3.4)% (p&lt;0.001), respectively. <b>Conclusions:</b> FOS supplementation increases faecal bifidobacteria concentrations and modifies mucosal dendritic cell function. This novel therapeutic strategy appears to decrease Crohn's disease activity in a small open label trial and therefore warrants further investigation.
SPECIFIC IMMUNE RESPONSE GENES OF THE GUINEA PIG
Authors: Harry G. Bluestein, Leonard Ellman, Ira Green, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1971)

The ability of guinea pigs to form immune responses specific for each of the random copolymers, L-glutamic acid and L-alanine (GA) and L-glutamic acid and L-tyrosine (GT), is under the control of distinct autosomal dominant genes. By testing for the ability to respond to these copolymers among the progeny from the reciprocal backcross mating of responder (2 x 13)F(1) animals with the appropriate nonresponder parental strain, we have demonstrated that different unigenic autosomal dominant traits control the ability to respond to GA and GT respectively. The data further shows that the GA gene is linked to the poly-L-lysine (PLL) gene and to the locus determining the major strain 2 histocompatibility specificities and that the GT gene is linked to the locus controlling the expression of major strain 13 histocompatibility specificities. Analysis of the inheritance of the GT and PLL genes among the offspring from a mating of responder (2 x 13)F(1) guinea pigs with random-bred guinea pigs unable to respond to GT or PLL demonstrate that these genes segregate away from each other. Thus, the PLL gene and the genes to which it is linked, the GA gene and the major strain 2 histocompatibility locus, behave as alleles or pseudoalleles to the GT gene and the major strain 13 histocompatibility locus.
Discriminant analysis on small cell lung cancer and non-small cell lung cancer by means of NSE and CYFRA-21.1
Authors: G Paone, G De Angelis, R Munno, G Pallotta, D Bigioni, C Saltini, A Bisetti, F Ameglio
Journal: European Respiratory Journal (1995)

A correct diagnosis of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) is essential both for prognostic and therapeutic reasons. We used discriminant analysis as a method to optimize the discriminant power of serum tumour marker levels for differentiation between SCLC and NSCLC. A panel of serum markers, including neurone specific enolase (NSE), cytokeratin fragment antigen 21.1 (CYFRA-21.1), tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA) was obtained in 50 consecutive NSCLC and 17 SCLC. Data were analysed by the BMDP statistical program after logarithmic transformation of marker levels. The variables selected were NSE and CYFRA-21.1. Considered together, they were able to give a 97% rate of correct classification. The formula generated (canonic variable, CV) was validated on a group of seven SCLC and 22 NSCLC patients. Only two errors occurred. We therefore conclude that the canonic variable tested, based on NSE and CYFRA-21.1, provides a good discrimination between the two types of lung cancer. The method is rapid, relatively inexpensive, and based on simple serum tests.
An inhibitor of sodium transport in the urine of dogs with normal renal function.
Authors: H Favre, K H Hwang, R W Schmidt, N S Bricker, J J Bourgoignie
Journal: Journal of Clinical Investigation (1975)

The urine and serum of chronically uremic patients and dogs contain an inhibitor of sodium transport that reduces short-circuit current (SCC) in the toad bladder and produces natriuresis in the rat. The present studies represent an effort to determine whether the same inhibitor is detectable in urine of normal dogs maintained on a dosium intake varying from 3 to 258 meq/day. Observations were made with and without fludrocortisone. The same Sephadex G-25 gel filtration fraction previously shown to contain the "uremic" inhibitor was tested in both the isolated toad bladder and rat bioassay systems. The fraction from dogs maintained on 258 meq qodium plus 0.2 mg fludrocortisone/day consistently inhibited SCC in the toad bladder and induced a natriuresis in the rat (P less than 0.001). The fraction from dogs on the same sodium intake without fludrocortisone was also natriuretic (P less than 0.01) but did not inhibit SCC significantly. In contrast, the fraction from dogs fed 3 meq sodium with fludrocortisone or 91 meq sodium without fludrocortisone had no significant effect in either assay system. Thus, an inhibitor of sodium transport has been found in the urine of nonuremic dogs. Both the degree of natriuresis in the rat and the degree of inhibition of SCC in the toad bladder correlated with the state of sodium balance which ensued in the dog.
Proliferation of Colo-357 Pancreatic Carcinoma Cells and Survival of Patients With Pancreatic Carcinoma Are Not Altered by Insulin Glargine
Authors: Saskia Erbel, Christina Reers, Volker W. Eckstein, Jörg Kleeff, Markus W. Büchler, Peter P. Nawroth, Robert A. Ritzel
Journal: Diabetes Care (2008)

OBJECTIVE—It was reported that the long-acting insulin analogue glargine induces cell proliferation in a human osteosarcoma cell line and therefore might induce or accelerate tumor growth. Induction of cell proliferation would be particularly relevant for insulin treatment of subjects with diabetes and the potential of bearing tumor cells (e.g., a history of a malignant disease). RESEARCH DESIGN AND METHODS—Proliferation, apoptosis, and the expression levels of insulin receptor, IGF-I receptor, and insulin receptor substrate (IRS) 2 were analyzed in human pancreatic cancer cells (Colo-357) after incubation (72 h) with insulin glargine or regular human insulin at 0–100 nmol/l. A total of 125 subjects, after partial or total pancreatectomy due to pancreatic carcinoma, were analyzed over a median follow-up period of 22 months. RESULTS—There was no significant difference between glargine and regular human insulin with respect to regulation of proliferation and apoptosis of Colo-357 cells. The expression levels of insulin receptor, IGF-I receptor, and IRS2 as a downstream molecule of both receptor signaling pathways were not altered at any concentration tested. The insulin receptor was downregulated to a similar degree by glargine and regular human insulin at high insulin concentrations (P &amp;lt; 0.0001 for glargine, P = 0.002 for regular human insulin). The median survival time after pancreatic surgery was 15 months. Survival analysis showed that the time-dependent proportion of patients who survived was identical in patients receiving insulin glargine versus insulin treatment without glargine and control subjects without diabetes after surgery (P = 0.4, three-sample comparison). CONCLUSIONS—Regular human insulin and insulin glargine may be used to treat diabetes in patients with pancreatic cancer.
Methodological and Conceptual Issues in Functional Magnetic Resonance Imaging: Applications to Schizophrenia Research
Authors: Gregory G. Brown, Lisa T. Eyler
Journal: Annual Review of Clinical Psychology (2006)

Functional magnetic resonance imaging (MRI) is a noninvasive, highly repeatable, and increasingly available method to study disordered brain activity among patients with psychological or neurological disorders. In this chapter the biophysical principles underlying functional MRI are presented, and methodological limitations of the method are discussed. Artifacts related to the biophysical basis of the functional MRI signal or associated with image acquisition methods are presented, as are artifacts related to baseline effects—especially those associated with medication, caffeine, and nicotine use. The difficulties associated with the comparison of groups of subjects differing in performance receive special attention. The limitations of cognitive subtraction designs for functional MRI are also discussed. Functional MRI studies of schizophrenia patients are used to illustrate these points.
Defaulting from V.D. Centres
Authors: C. H. Wilkie
Journal: BMJ (1939)

2. Age at Onset of Disease.-There was no association, as is illustrated by the following table: Age at Onset No. of Cases Mean Binet I.Q.Less than 4 years 30 104.1 4-7 years 32 103.8 8-14 years 36 103.9Total 98 103.9 3. Interval between Onset of Disease and Performance of Test.-Once again there was no association.Interval between Onset of No. of Cases Mean Binet I.Q.Disease and Test 0-1 months .21104.5 1-4 Years .38 103.7 5-15 vears .39103.8Total .98 103.9Thus there is no evidence either of a depression of intelligence which passes off or of a depression which is produced by the after-effects during the years of childhood.4. Occurrence of Clinically Recognizable Cerebral Symptonms at Onset of Disease.
Phosphatidylinositol Triphosphate Kinase-dependent and c-Jun NH2-Terminal Kinase-dependent Induction of Telomerase by Calcium Requires Pyk2
Authors: Michelle Y. Alfonso-De Matte, Patricia A. Kruk
Journal: Cancer Research (2004)

Abstract Calcium signaling has been linked to activation of Pyk2, a calcium-dependent, focal adhesion kinase-related, non-receptor tyrosine kinase. Signaling via Pyk2 can activate c-jun NH2-terminal kinase (JNK). Calcium has also been shown to activate phosphatidylinositol triphosphate kinase and/or JNK. Here, we show that calcium signaling in ovarian surface epithelial cells not only induces telomerase activity via JNK but also activates Pyk2. Moreover, telomerase activation by Pyk2 requires JNK activation. In contrast, a kinase-deficient Pyk2 construct failed to activate either JNK or telomerase. Finally, we demonstrate that Pyk2 is capable of driving the human telomerase reverse transcriptase promoter, resulting in telomerase activation. These data suggest a novel role of Pyk2 for telomerase regulation.
Alternative and complementary medicine for asthma.
Authors: D J Lane, T V Lane
Journal: Thorax (1991)

EditorialsAlternative and complementary medicine for asthma It may well be asked what reasons there could be for exposing the pages of Thorax to a critique of alternative and complementary medicine.Two spring to mind: scientific curiosity and consumer demand.Alternative medicine makes claims that orthodox medical science cannot com- prehend.'Yet there is sufficient published evidence to suggest that some forms of alternative medicine have measurable therapeutic effects.There is also widespread enthusiasm among the public for alternatives to conven- tional treatment" and sufficient interest from clinicians, especially general practitioners,5 to make it important for the subject to be examined critically.This review will focus on asthma, looking at a wide range of alternative and complementary approaches.
The Functional <b> <i>UGT1A1</i> </b> Promoter Polymorphism Decreases Endometrial Cancer Risk
Authors: Yannick Duguay, Monica McGrath, Johanie Lépine, Jean-François Gagné, Susan E. Hankinson, Graham A. Colditz, David J. Hunter, Marie Plante, Bernard Têtu, Alain Bélanger, Chantal Guillemette, Immaculata De Vivo
Journal: Cancer Research (2004)

Abstract UDP-glucuronosyltransferase (UGT) 1A1 is involved in the inactivation of estradiol (E2) and its oxidized metabolites. These metabolites have been shown to contribute to the development of endometrial cancer in animal studies. Thus UGT1A1 represents a candidate gene in endometrial carcinogenesis. In this study, we established the substrate specificity of UGT1A1 for E2 and its 2- and 4-hydroxylated metabolites. Intrinsic clearances indicated that UGT1A1 had a preference for the glucuronidation of 2-hydroxyestradiol, a metabolite associated with antiproliferative activity. Expression analysis demonstrated that UGT1A1 is present in the nonmalignant endometrium. Subsequently, we sought to determine whether the common UGT1A1 promoter allele, UGT1A1*28 [A(TA)7TAA], which decreases gene transcription, was associated with endometrial cancer risk in a case-control study nested within the Nurses’ Health Study (222 cases, 666 matched controls). Conditional logistic regression demonstrated a significant inverse association with the UGT1A1*28 allele and endometrial cancer risk. Compared with women homozygous for the UGT1A1*1 [A(TA)6TAA] allele, the adjusted odds ratio (OR) was 0.81 [95% confidence interval (CI), 0.56–1.16] for the UGT1A1*1/*28 genotype and 0.40 (95% CI, 0.21–0.75) for the homozygous UGT1A1*28 genotype (Ptrend = 0.007). There was a suggestion of an interaction by menopausal status [OR = 0.39 (95% CI, 0.18–0.85) for premenopausal women and OR = 0.79 (95% CI, 0.55–1.13) for postmenopausal women who carry the UGT1A1*28 allele (Pinteraction = 0.05)]. These observations suggest that lower expression of UGT1A1 decreases the risk of endometrial cancer by reducing the excretion of 2-hydroxyestradiol, the antiproliferative metabolite of E2, in the endometrium.
Insulin-like growth factor-I gene therapy reverses morphologic changes and reduces hyperprolactinemia in experimental rat prolactinomas
Authors: Gloria M Console, Claudia B Herenu, Gisela A Camihort, Georgina C Luna, Maria I Bracamonte, Gustavo R Morel, Rodolfo G Goya
Journal: Molecular Cancer (2008)

The implementation of gene therapy for the treatment of pituitary tumors emerges as a promising complement to surgery and may have distinct advantages over radiotherapy for this type of tumors. Up to now, suicide gene therapy has been the main experimental approach explored to treat experimental pituitary tumors. In the present study we assessed the effectiveness of insulin-like growth factor I (IGF-I) gene therapy for the treatment of estrogen-induced prolactinomas in rats. Female Sprague Dawley rats were subcutaneously implanted with silastic capsules filled with 17-β estradiol (E2) in order to induce pituitary prolactinomas. Blood samples were taken at regular intervals in order to measure serum prolactin (PRL). As expected, serum PRL increased progressively and 23 days after implanting the E2 capsules (Experimental day 0), circulating PRL had undergone a 3–4 fold increase. On Experimental day 0 part of the E2-implanted animals received a bilateral intrapituitary injection of either an adenoviral vector expressing the gene for rat IGF-I (RAd-IGFI), or a vector (RAd-GFP) expressing the gene for green fluorescent protein (GFP). Seven days post vector injection all animals were sacrificed and their pituitaries morphometrically analyzed to evaluate changes in the lactotroph population. RAd-IGFI but not RAd-GFP, induced a significant fall in serum PRL. Furthermore, RAd-IGFI but not RAd-GFP significantly reversed the increase in lactotroph size (CS) and volume density (VD) induced by E2 treatment. We conclude that IGF-I gene therapy constitutes a potentially useful intervention for the treatment of prolactinomas and that bioactive peptide gene delivery may open novel therapeutic avenues for the treatment of pituitary tumors.
Bookmarking Target Genes in Mitosis: A Shared Epigenetic Trait of Phenotypic Transcription Factors and Oncogenes?
Authors: Sayyed K. Zaidi, Rodrigo A. Grandy, Cesar Lopez-Camacho, Martin Montecino, Andre J. van Wijnen, Jane B. Lian, Janet L. Stein, Gary S. Stein
Journal: Cancer Research (2014)

The regulatory information for phenotype, proliferation, and growth of normal and tumor cells must be maintained through genome replication in the S phase and cell division during mitosis. Epigenetic mechanisms that include DNA methylation, posttranslational modifications of histones, selective utilization of histone variants, and inheritable RNA molecules play pivotal roles in maintaining cellular identity through mitotic divisions. Recent studies demonstrate that mitotic occupancy of genes, which are determinants of cell fate, growth, and proliferation, by lineage-restricted transcription factors is a key epigenetic mechanism for retention and transmission of cellular expression memory. Evidence is emerging for the presence of distinct transcriptional regulatory microenvironments in mitotic chromosomes in which the genes bookmarked for reactivation postmitotically reside. Importantly, some oncoproteins are present in mitotic microenvironments where they occupy target genes during mitosis and may contribute to perpetuating the transformed phenotype. We discuss emerging regulatory implications of epigenetically bookmarking genes during mitosis for physiologic control as well as for the onset and progression of cancer.
1117-88 High-density lipoprotein, but not low-density lipoprotein cholesterol levels influence short-term prognosis after acute coronary syndrome: Results from the MIRACL trial
Authors: Anders G Olsson, Gregory G Schwartz, Michael D Ezekowitz, Peter Ganz, Michael F Oliver, David Waters, Andreas Zeiher, William Sasiela, Michael Szarek
Journal: Journal of the American College of Cardiology (2004)
Neurocognitive Dysfunction in First-Episode Psychosis: Correlates With Symptoms, Premorbid Adjustment, and Duration of Untreated Psychosis
Authors: Bjørn Rishovd Rund, Ingrid Melle, Svein Friis, Tor K Larsen, Liv Jaeger Midbøe, Stein Opjordsmoen, Erik Simonsen, Per Vaglum, Thomas McGlashan
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The authors examined the relationship of neurocognitive function with duration of untreated psychosis, premorbid illness factors, and clinical symptoms to determine whether long duration of untreated psychosis independently compromises cognitive function. METHOD: Patients recruited to a study of the effect of an early detection program on the duration of untreated first-episode psychosis in two catchment areas were compared to patients in a similar treatment program in two other catchment areas without an early detection program. The median duration of untreated psychosis was 10.5 weeks for all patients. A total of 301 patients entered the study, and 207 completed a comprehensive neuropsychological test battery that assessed working memory/fluency, executive function, verbal learning, impulsivity, and motor speed. The median time from start of treatment to neuropsychological testing was 108 days; all patients were tested within 9 months. RESULTS: No significant association was found between duration of untreated psychosis and any of the cognitive measures. Strong associations were demonstrated between poorer premorbid school functioning and neurocognitive deficits, especially in verbal learning and working memory. No relationship was found between neurocognitive functions and clinical measures, except for an inverse correlation of Positive and Negative Syndrome Scale negative symptoms and working memory and a positive correlation between positive symptoms and motor speed. CONCLUSIONS: The data contribute to a disconfirmation of the hypothesis of an association between duration of untreated psychosis and neurocognitive performance at baseline.
Mass Diseases, Mass Exposures, and Mass Media
Authors: Thomas A. Farley
Journal: JAMA Internal Medicine (2015)

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