tbuckley/cabot-search huggingface dataset:
Dietary patterns and respiratory symptoms in pre-school children: the Generation R Study
Authors: Ilse I.M. Tromp, Jessica C. Kiefte-de Jong, Jeanne H. de Vries, Vincent W.V. Jaddoe, Hein Raat, Albert Hofman, Johan C. de Jongste, Henriette A. Moll
Journal: European Respiratory Journal (2012)

Overall diet in early childhood may affect the development of respiratory symptoms. This study examined whether childhood dietary patterns are associated with respiratory symptoms in Dutch pre-school children, and whether this association could be explained by energy intake. A prospective cohort study was performed in 2,173 children aged ≤4 yrs. Data on asthma-related symptoms were obtained by questions from the age-adapted version of the "International Study of Asthma and Allergies in Childhood" questionnaires. Data on respiratory tract infections, defined as episodes of physician attended fever with respiratory symptoms, was obtained by questionnaire. Principal components analysis was used to develop dietary patterns at 14 months of age. Compared with low adherence, high adherence to the “Western” dietary pattern was significantly associated with frequent wheeze at 3 yrs of age (relative risk (RR) 1.39, 95% CI 1.02–1.89) and frequent shortness of breath (RR 1.44, 95% CI 1.03–2.01) and respiratory tract infections (RR 1.54, 95% CI 1.08–2.19) at 4 yrs of age. However, this association was partially explained by energy intake. A “Western” diet may increase the risk of frequent respiratory symptoms at 3 and 4 yrs of age. In some measure, this association was explained by energy intake.
Electrogenic glucose absorption in untreated and treated coeliac disease.
Authors: N W Read, R J Levin, C D Holdsworth
Journal: Gut (1976)

Using a method for measuring changes in transmural potential difference across the human jejunum in vivo, the operational kinetic parameters of 'Apparent Km' and PD max for the active electrogenic component of glucose absorption were estimated in a group of healthy volunteers and in patients with coeliac disease. Both the 'Apparent Km' (17+/2mM; mean +/SEM) and the PD max (8.6+/0.7 mV) in nine patients with untreated coeliac disease were significantly lower (p less than 0.005) than in the control group ('Apparent Km' = 74+/5mM; PD max 12.8+/0.9mV, n=20). Treatment of five coeliac patients by gluten withdrawal for less than three months increased significantly the values of both the "Apparent Km (35+/6mM) and the TPD max (11.4+/1.2mV). Treatment of five patients for more than six months caused a further increase in the values of both kinetic parameters ('Apparent Km' = 108+/13mM; PD max =15.6+/2.7mV) to levels which exceeded those in healthy subjects. The possible interpretations of the differences in the kinetic characteristics of electrogenic glucose transport between coeliac patients and healthy subjects are discussed.
A Phase I Study of the HSP90 Inhibitor Retaspimycin Hydrochloride (IPI-504) in Patients with Gastrointestinal Stromal Tumors or Soft-Tissue Sarcomas
Authors: Andrew J. Wagner, Rashmi Chugh, Lee S. Rosen, Jeffrey A. Morgan, Suzanne George, Michael Gordon, Joi Dunbar, Emmanuel Normant, David Grayzel, George D. Demetri
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Heat shock protein 90 (HSP90) is required for the proper folding, function, and stability of various client proteins, two of which (KIT and PDGFRα) are critical in the pathogenesis and progression of gastrointestinal stromal tumors (GIST). This phase I study investigated the safety and maximum tolerated dose (MTD) of retaspimycin hydrochloride (IPI-504), a novel potent and selective HSP90 inhibitor, in patients with metastatic and/or unresectable GIST or other soft-tissue sarcomas (STS). Experimental Design: IPI-504 was administered intravenously at doses ranging from 90 to 500 mg/m2 twice weekly for 2 weeks on/1 week off. Safety, pharmacokinetic, and pharmacodynamic profiles were determined. Response was assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.0 and optionally via 18-fluorodeoxyglucose positron emission tomography (18-FDG-PET) imaging. Results: Fifty-four patients received IPI-504; 37 with GIST and 17 with other STS. The MTD was 400 mg/m2 twice weekly for 2 weeks on/1 week off. Common related adverse events were fatigue (59%), headache (44%), and nausea (43%). Exposure to IPI-504, 17-AAG, and 17-AG increased with IPI-504 dose. Stable disease (SD) was observed in 70% (26 of 37) of patients with GIST and 59% (10 of 17) of patients with STS. There was one confirmed partial response (PR) in a patient with GIST and one PR in a patient with liposarcoma. Metabolic partial responses occurred in 11 of 29 (38%) patients with GIST. Conclusions: In this study of advanced GIST or other STS, IPI-504 was generally well-tolerated with some evidence of antitumor activity, serving as a clinical proof-of-concept that HSP90 inhibition remains a promising strategy. Clin Cancer Res; 19(21); 6020–9. ©2013 AACR.
Adiponectin Inhibits Endothelial Synthesis of Interleukin-8
Authors: Chikaaki Kobashi, Masaharu Urakaze, Mika Kishida, Etsuko Kibayashi, Hideki Kobayashi, Shinji Kihara, Tohru Funahashi, Michiyo Takata, Rie Temaru, Akira Sato, Katsuya Yamazaki, Norio Nakamura, Masashi Kobayashi
Journal: Circulation Research (2005)

Adiponectin is an antiatherogenic adipokine that inhibits inflammation by mechanisms that are not completely understood. We explored the effect of adiponectin on endothelial synthesis of interleukin-8 (IL-8), a pro-inflammatory chemokine that plays a role in atherogenesis. Adiponectin decreased the secretion of IL-8 from human aortic endothelial cells (HAEC) stimulated with tumor necrosis factor-alpha (TNF-alpha). Adiponectin also inhibited IL-8 mRNA expression induced by TNF-alpha. Phosphorylation of IkappaB-alpha was decreased by adiponectin, but phosphorylation of ERK, SAPK/JNK, and p38MAPK were unaffected. Adiponectin increased intra-cellular cAMP levels in HAEC in a dose-dependent manner; PKA activity was also increased. The inhibitory effect of adiponectin on TNF-alpha-induced IL-8 synthesis was inhibited by pretreatment with Rp-cAMP, a PKA inhibitor. These observations suggest that adiponectin inhibits IL-8 synthesis through inhibition of a PKA dependent NF-kappaB signaling pathway. We also showed that adiponectin enhances Akt phosphorylation. The inhibitory effect of adiponectin on TNF-alpha-induced IL-8 synthesis was abrogated in part by pretreatment with the PI3 kinase inhibitor LY294002 or by Akt siRNA transfection, suggesting that Akt activation might inhibit IL-8 synthesis induced by TNF-alpha. We conclude that inhibition of NF-kappaB and activation of Akt phosphorylation may mediate adiponectin inhibition of atherosclerosis.
THE AETIOLOGY AND TREATMENT OF CHILDREN'S PHOBIAS: A REVIEW
Authors: S. RACHMAN, C. G. COSTELLO
Journal: American Journal of Psychiatry (1961)

Mention has been made of Mary Cover Jones's(20, 21) classic studies in which she describes her attempt to develop techniques for eliminating children's fears. The signfficance of this early work is only now becoming recognized. She gives an account of several methods of treatment. Four of these appear to be promising, practical and in accord with present-day learning theory. They are the methods of: 1. Direct conditioning. 2. Social imitation. 3. Systematic distraction and 4. Feeding responses. The fruitfulness of the behavior theory approach to phobias is well demonstrated if we add to Jones' list the additional new methods which have been, or could be used in overcoming children's phobias. 5. Systematic desensitization (Wolpe) 6. Assertive responses (Wolpe) 7. Relaxation responses (Wolpe) 8. "Pleasant" responses in the life situation–with drug enhancement (Wolpe) In a suggestive article by Jersild and Holmes(17) further possible methods for treatment of children's fears are discussed. From their survey of parent's experiences in dealing with children's fears, Jersild and Holmes suggest these techniques (among others) : Prompting the child to acquire skills which will enable him to cope with the feared situation; progressive contact with, and participation in, the feared situation; verbal explanation and reassurance; practical demonstration of fearlessness. Some of these techniques are already employed by prevailing therapies without receiving explicit acknowledgement. All these methods certainly provide therapists with a formidable armamentarium to begin with. What is now required is careful, thorough investigation of these methods and above all a major project to establish the degree and permanence of improvements which may be obtained by these techniques. In the meantime, active therapists may consider conducting their own investigations of these methods when faced with children suffering from phobic conditions. Obviously the choice of the method will depend to a considerable extent on the nature of the phobia. It is worth remembering also that these methods are not mutually exclusive and it is probable that in many cases a combination of these techniques may offer the most promising approach.
Attenuation of alcohol-induced hepatic fibrosis by polyunsaturated lecithin
Authors: Charles S. Lieber, Leonore M. Decarli, Ki M. Mak, Cho-Il Kim, Maria A. Leo
Journal: Hepatology (1990)

Characteristic features of alcoholic liver injury include fibrosis and striking membrane alterations, with associated phospholipid changes. To offset some of these abnormalities, a 10-yr study was conducted in baboons: 12 animals (eight females, four males) were fed a liquid diet supplemented with polyunsaturated lecithin (4.1 mg/kcal) for up to 8 yr, with either ethanol (50% of total energy) or isocaloric carbohydrate. They were compared with another group of 18 baboons fed an equivalent amount of the same diet (with or without ethanol), but devoid of lecithin. In the two groups, comparable increases in lipids developed in the ethanol-fed animals, but striking differences in the degree of fibrosis were seen. Whereas at least septal fibrosis (with cirrhosis in two) and transformation of their lipocytes into transitional cells developed in seven of the nine baboons fed the regular diet with ethanol, septal fibrosis did not develop in any animals fed lecithin (p &lt; 0.005). They did not progress beyond the stage of perivenular fibrosis (sometimes associated with pericellular and perisinusoidal fibrosis) and had a significantly lesser activation of lipocytes to transitional cells. Furthermore, when three of these animals were taken off lecithin, but continued on the same amount of the ethanol-containing diet, they rapidly (within 18 to 21 mo) progressed to cirrhosis, accompanied by an increased transformation of their lipocytes to transitional cells. These results indicate that some component of lecithin exerts a protective action against the fibrogenic effects of ethanol. Because we had previously found that choline, in amounts present in lecithin, has no comparable action, the polyunsaturated phospholipids themselves might be responsible for the protective effect. (HEPATOLOGY 1990;12:1390-1398).
Dynamic Gene Copy Number Variation in Collinear Regions of Grass Genomes
Authors: J.-H. Xu, J. L. Bennetzen, J. Messing
Journal: Molecular Biology and Evolution (2011)

A salient feature of genomes of higher organisms is the birth and death of gene copies. An example is the alpha prolamin genes, which encode seed storage proteins in grasses (Poaceae) and represent a medium-size gene family. To better understand the mechanism, extent, and pace of gene amplification, we compared prolamin gene copies in the genomes of two different tribes in the Panicoideae, the Paniceae and the Andropogoneae. We identified alpha prolamin (setarin) gene copies in the diploid foxtail millet (Paniceae) genome (490 Mb) and compared them with orthologous regions in diploid sorghum (730 Mb) and ancient allotetraploid maize (2,300 Mb) (Andropogoneae). Because sequenced genomes of other subfamilies of Poaceae like rice (389 Mb) (Ehrhartoideae) and Brachypodium (272 Mb) (Pooideae) do not have alpha prolamin genes, their collinear regions can serve as "empty" reference sites. A pattern emerged, where genes were copied and inserted into other chromosomal locations followed by additional tandem duplications (clusters). We observed both recent (species-specific) insertion events and older ones that are shared by these tribes. Many older copies were deleted by unequal crossing over of flanking sequences or damaged by truncations. However, some remain intact with active and inactive alleles. These results indicate that genomes reflect only a snapshot of the gene content of a species and are far less static than conventional genetics has suggested. Nucleotide substitution rates for active alpha prolamins genes were twice as high as for low copy number beta, gamma, and delta prolamin genes, suggesting that gene amplification accelerates the pace of divergence.
Several Carcinoembryonic Antigens (CD66) Serve as Receptors for Gonococcal Opacity Proteins
Authors: Tie Chen, Fritz Grunert, Andrew Medina-Marino, Emil C. Gotschlich
Journal: The Journal of Experimental Medicine (1997)

Neisseria gonorrhoeae (GC) is a human pathogen that adheres to and invades genital surfaces. Although pili are required for the initial adherence, the interaction of GC with epithelial cells is also promoted by a family of outer membrane proteins, the opacity (Opa) proteins such as OpaA protein from strain MS11. Studies have demonstrated that the interaction of the OpaA GC with epithelial cells involves binding to heparan sulfate attached to syndecan receptors. However, other Opa proteins interact with CEA gene family member 1 (CGM1) or biliary glycoprotein (BGP), members of the CD66 antigen family. In this study, we demonstrate that, in addition, the 180-kD carcinoembryonic antigen (CEA) is a receptor for Opa proteins. This conclusion was based on the following observations. First, transfected HeLa cells expressing CEA (HeLaCEA) and the CEA-expressing colon cancer cell line (LS 174T) bound and subsequently engulfed the Opa+ bacteria. These interactions were inhibited by anti-CEA antibody, but could not be inhibited by addition of heparin. Furthermore, OpaI E. coli directly bound purified CEA. We also compared the adherence and invasion by Opa+ bacteria of CD66 transfected HeLa cells: HeLa-BGPa, HeLa-CGM6, HeLa-NCA, HeLa-CGM1a, HeLa-CEA, and HeLa-Neo serving as negative control. Using OpaI as the prototype, the relative ability of the transfected HeLa cell lines to support adherence was (CEA = BGPa &amp;gt;CGM1a &amp;gt;NCA &amp;gt;&amp;gt;CGM6 = Neo). The ability to mediate invasion of the transfectant cells was (CGM1a &amp;gt;CEA &amp;gt;BGPa &amp;gt;NCA &amp;gt;CGM6 = Neo). Among the Opa proteins tested, OpaC proved to be bifunctional, able to mediate adherence to both syndecan receptors and to CD66 antigens.
CpG Oligodeoxynucleotides Act as Adjuvants that Switch on T Helper 1 (Th1) Immunity
Authors: Rose S. Chu, Oleg S. Targoni, Arthur M. Krieg, Paul V. Lehmann, Clifford V. Harding
Journal: The Journal of Experimental Medicine (1997)

Synthetic oligodeoxynucleotides (ODN) that contain unmethylated CpG motifs (CpG ODN) induce macrophages to secrete IL-12, which induces interferon (IFN)-γ secretion by natural killer (NK) cells. Since these cytokines can induce T helper 1 (Th1) differentiation, we examined the effects of coadministered CpG ODN on the differentiation of Th responses to hen egg lysozyme (HEL). In both BALB/c (Th2-biased) and B10.D2 (Th1-biased) mice, immunization with HEL in incomplete Freund's adjuvant (IFA) resulted in Th2-dominated immune responses characterized by HEL-specific secretion of IL-5 but not IFN-γ. In contrast, immunization with IFA-HEL plus CpG ODN switched the immune response to a Th1-dominated cytokine pattern, with high levels of HEL-specific IFN-γ secretion and decreased HEL-specific IL-5 production. IFA-HEL plus CpG ODN also induced anti-HEL IgG2a (a Th1-associated isotype), which was not induced by IFA-HEL alone. Control non–CpG ODN did not induce IFN-γ or IgG2a, excepting lesser increases in B10.D2 (Th1-biased) mice. Thus, CpG ODN provide a signal to switch on Th1-dominated responses to coadministered antigen and are potential adjuvants for human vaccines to elicit protective Th1 immunity.
Safety and efficacy of measles, mumps, and rubella vaccine in patients with DiGeorge syndrome
Authors: Nashat Al-Sukaiti, Brenda Reid, Sasson Lavi, Daifulah Al-Zaharani, Adelle Atkinson, Chaim M. Roifman, Eyal Grunebaum
Journal: Journal of Allergy and Clinical Immunology (2010)
Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years
Authors: William W. Thompson, Cristofer Price, Barbara Goodson, David K. Shay, Patti Benson, Virginia L. Hinrichsen, Edwin Lewis, Eileen Eriksen, Paula Ray, S. Michael Marcy, John Dunn, Lisa A. Jackson, Tracy A. Lieu, Steve Black, Gerrie Stewart, Eric S. Weintraub, Robert L. Davis, Frank DeStefano
Journal: New England Journal of Medicine (2007)

It has been hypothesized that early exposure to thimerosal, a mercury-containing preservative used in vaccines and immune globulin preparations, is associated with neuropsychological deficits in children.We enrolled 1047 children between the ages of 7 and 10 years and administered standardized tests assessing 42 neuropsychological outcomes. (We did not assess autism-spectrum disorders.) Exposure to mercury from thimerosal was determined from computerized immunization records, medical records, personal immunization records, and parent interviews. Information on potential confounding factors was obtained from the interviews and medical charts. We assessed the association between current neuropsychological performance and exposure to mercury during the prenatal period, the neonatal period (birth to 28 days), and the first 7 months of life.Among the 42 neuropsychological outcomes, we detected only a few significant associations with exposure to mercury from thimerosal. The detected associations were small and almost equally divided between positive and negative effects. Higher prenatal mercury exposure was associated with better performance on one measure of language and poorer performance on one measure of attention and executive functioning. Increasing levels of mercury exposure from birth to 7 months were associated with better performance on one measure of fine motor coordination and on one measure of attention and executive functioning. Increasing mercury exposure from birth to 28 days was associated with poorer performance on one measure of speech articulation and better performance on one measure of fine motor coordination.Our study does not support a causal association between early exposure to mercury from thimerosal-containing vaccines and immune globulins and deficits in neuropsychological functioning at the age of 7 to 10 years.
Chronic liver disease in the extremely elderly of 80 years or more: clinical characteristics, prognosis and patient survival analysis
Authors: Yujin Hoshida, Kenji Ikeda, Masahiro Kobayashi, Yoshiyuki Suzuki, Akihito Tsubota, Satoshi Saitoh, Yasuji Arase, Mizuho Kobayashi, Naoya Murashima, Kazuaki Chayama, Hiromitsu Kumada
Journal: Journal of Hepatology (1999)
The use of ancrod to prevent thrombosis on prosthetic heart valves: An experimental study
Authors: M. P. Singh, H. H. Bentall, W. R. Bell, E. G. J. Olsen, S. P. Allwork
Journal: Thorax (1970)

Ancrod (Arvin) on slow intravenous administration converts fibrinogen into fibrin at a rate which does not cause intravascular thrombosis. The fibrin is eliminated from the circulation and the blood is thus rendered incoagulable. To test the efficacy of ancrod in the prevention of thrombosis after prosthetic replacement of the heart valves, the tricuspid valve was replaced with a polypropylene mitral valve in 17 calves, using cardiopulmonary bypass. Five calves were eliminated from the study. Eleven calves were treated with ancrod, and one untreated calf was used as a control. Four out of five prosthetic valves in calves treated with ancrod for up to 72 hours were free of thrombus formation, and one out of three at one week. In the long-term study, fibrinogen titres rose after varying intervals, in spite of continual treatment with ancrod. This `escape9 of fibrinogen titres from the control of ancrod may be due to species resistance or to the development of immunity. Further study is in progress to elucidate this point and to gain further knowledge for the clinical application of ancrod.
The prognosis of early mycosis fungoides is not influenced by phenotype and T-cell clonality
Authors: C. Massone, G. Crisman, H. Kerl, L. Cerroni
Journal: British Journal of Dermatology (2008)

The influence of phenotype and detection of clonality on prognosis in early mycosis fungoides has never been addressed in large studies.To correlate immunophenotype and detection of clonality with clinical outcome.We analysed 73 biopsy specimens from 68 patients with early mycosis fungoides (stage Ia or Ib) and at least 10 years of follow up (or dead of disease).Four phenotypic groups could be identified: group A (alpha/beta+ CD4+ CD8- TIA1-), 51 patients; median survival time 160 months; group B (alpha/beta+ CD4- CD8+ TIA1+), 10 patients; median survival time 195 months; group C (alpha/beta- CD4- CD8+/- TIA1+), five patients; median survival time 165 months; and group D (alpha/beta+ CD4- CD8- TIA1-), two patients; median survival time 130 months. Survival curves did not show statistical differences among the groups. Monoclonality was detected in 36 of 67 tested biopsies (54%), and statistical analyses did not show prognostic differences between the clonal and nonclonal cases.We conclude that cytotoxic phenotype and detection of monoclonal T-cell receptor-gamma gene rearrangement in early lesions of mycosis fungoides do not have any prognostic significance.
Reversal of Secondary Hyperparathyroidism by Cimetidine in Chronically Uremic Dogs
Authors: Allan I. Jacob, Janet M. Canterbury, George Gavellas, Phillip W. Lambert, Jacques J. Bourgoignie
Journal: Journal of Clinical Investigation (1981)

Chronic cimetidine therapy has been shown to suppress circulating concentrations of immunoreactive parathyroid hormone (iPTH) in hemodialysis patients. To evaluate the long-term metabolic effects of cimetidine treatment, we studied seven chronically uremic dogs for 20 wk. The dogs were studied under metabolic conditions before, during, and after cimetidine therapy. iPTH fell progressively in the five treated dogs from 536±70 μleq/ml (mean±SE) (nl < 100 μleq/ml) before treatment to 291±25 μleq/ml at 12 wk (P < 0.001) and 157±32 μleq/ml at 20 wk (P < 0.001). The control dogs showed no consistent change in iPTH. The fall in iPTH was not associated with a change in serum ionized calcium. However, serum phosphorus decreased from 5.7±0.9 mg/dl to 3.4±0.2 mg/dl by the 20th wk (P < 0.05). By contrast, the serum concentration of 1,25-dihydroxycholecalciferol increased in all treated dogs from 33.4±4.3 pg/ml to 51.8±2.4 pg/ml during treatment (P < 0.01). Calcium balance was negative in all seven dogs before cimetidine (−347±84 mg/72 h) and remained so in the control dogs; it became positive in the five treated dogs after 12 wk (1,141±409 mg/72 h) (P < 0.05). Phosphorus balance, 24-h fractional phosphate excretion, and creatinine clearance remained unchanged. Pooled samples of serum obtained during the control and 20th wk of therapy were fractionated by gel filtration and the eluates assayed for immunoreactivity. The decrease in iPTH was associated with a decrease in all the immunoreactive species, indicating suppression of parathyroid gland secretion.