tbuckley/cabot-search huggingface dataset:
Inhibitory effects of hypermagnesemia on the renal action of parathyroid hormone.
Authors: E Slatopolsky, A Mercado, A Morrison, J Yates, S Klahr
Journal: Journal of Clinical Investigation (1976)

Available evidence indicates that serum magnesium (Mg++) levels influence the secretion rate of parathyroid hormone (PTH). Whether serum Mg++ concentrations also modify the action of PTH on its target organs has not been definitively established. The present experiments were designed to study this possibility. The effect of infusing PTH on the urinary excretion of cyclic AMP (cAMP) and PO4= was examined in five normal dogs at two different levels of serum Mg++. At normal serum Mg++ concentrations (1.89 +/- 0.14 mg/100 ml), PTH infusion increased cAMP excretion from 1.76 +/- 0.27 to 4.87 +/- 1.00 nmol/min and fractional PO4= excretion (FEPO4) from 1.58 +/- 0.36% to 23.1 +/- 2.17%. When an identical amount of PTH was given to the same dogs at a serum Mg++ of 4.36 +/- 0.20 mg/100 ml, FEPO4 increased to only 6.02+/-1.89% and cAMP from 1.31 +/- 0.23 to 1.89 +/- 0.39 nmol/min. Identical results were obtained in thyroparathyroidectomized hypermagnesemic dogs. Increased serum Mg++ levels had no effect on the phosphaturia produced by the infusion of dibutyryl cAMP to thyroparathyroidectomized dogs. In vitro studies using rat renal cortical slices revealed a progressive decrease in cAMP production in response to PTH as the Mg++ concentrations were increased in the incubation medium. The overall results indicate that hypermagnesemia inhibits the phosphaturic response to PTH by decreasing the renal production of cAMP. Plasma magnesium, therefore, may participate in a double feedback mechanism, not only controlling the release of PTH, but also altering the biological activity of the hormone at the level of the target organ.
Sex-related differences in COPD in five Latin American cities: the PLATINO study
Authors: M.V. Lopez Varela, M. Montes de Oca, R.J. Halbert, A. Muiño, R. Perez-Padilla, C. Tálamo, J.R.B. Jardim, G. Valdivia, J. Pertuzé, D. Moreno, A.M.B. Menezes
Journal: European Respiratory Journal (2010)

There is evidence to suggest sex differences exists in chronic obstructive pulmonary disease (COPD) clinical expression. We investigated sex differences in health status perception, dyspnoea and physical activity, and factors that explain these differences using an epidemiological sample of subjects with and without COPD. PLATINO is a cross-sectional, population-based study. We defined COPD as post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ratio &lt;0.70, and evaluated health status perception (Short Form (SF)-12 questionnaire) and dyspnoea (Medical Research Council scale). Among 5,314 subjects, 759 (362 females) had COPD and 4,555 (2,850 females) did not. In general, females reported more dyspnoea and physical limitation than males. 54% of females without COPD reported a dyspnoea score ≥2 versus 35% of males. A similar trend was observed in females with COPD (63% versus 44%). In the entire study population, female sex was a factor explaining dyspnoea (OR 1.60, 95%CI 1.40–1.84) and SF-12 physical score (OR -1.13, 95%CI -1.56– -0.71). 40% of females versus 28% of males without COPD reported their general health status as fair-to-poor. Females with COPD showed a similar trend (41% versus 34%). Distribution of COPD severity was similar between sexes, but currently smoking females had more severe COPD than currently smoking males. There are important sex differences in the impact that COPD has on the perception of dyspnoea, health status and physical activity limitation.
THE EFFECT OF UNILATERAL NEPHRECTOMY ON THE SENILE ATROPHY OF THE KIDNEY IN THE WHITE RAT
Authors: Robert A. Moore, Louis M. Hellman
Journal: The Journal of Experimental Medicine (1930)

1. In senility in the white rat there is a decrease in the total number of glomerular units. 2, The decrease in glomerular units is associated with an increase in the average diameter and a greater variation in size, of the remaining glomeruli. 3. Unilateral nephrectomy during adult life has no effect on these senile changes.
Breathing patterns during sleep in patients with nocturnal asthma.
Authors: A D Morgan, G B Rhind, J J Connaughton, J R Catterall, C M Shapiro, N J Douglas
Journal: Thorax (1987)

<h3>Objective</h3> Sugar-sweetened beverages (SSBs) are associated with hyperuricaemia and gout. Whether other important food sources of fructose-containing sugars share this association is unclear. <h3>Design</h3> To assess the relation of important food sources of fructose-containing sugars with incident gout and hyperuricaemia, we conducted a systematic review and meta-analysis of prospective cohort studies. <h3>Methods</h3> We searched MEDLINE, Embase and the Cochrane Library (through 13 September 2017). We included prospective cohort studies that investigated the relationship between food sources of sugar and incident gout or hyperuricaemia. Two independent reviewers extracted relevant data and assessed the risk of bias. We pooled natural-log transformed risk ratios (RRs) using the generic inverse variance method with random effects model and expressed as RR with 95% confidence intervals (CIs). The overall certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation system. <h3>Results</h3> We identified three studies (1 54 289 participants, 1761 cases of gout), comparing the highest with the lowest level of exposure for SSBs, fruit juices and fruits. No reports were found reporting incident hyperuricaemia. Fruit juice and SSB intake showed an adverse association (fruit juice: RR=1.77, 95% CI 1.20 to 2.61; SSB: RR=2.08, 95% CI 1.40 to 3.08), when comparing the highest to lowest intake of the most adjusted models. There was no significant association between fruit intake and gout (RR 0.85, 95% CI 0.63 to 1.14). The strongest evidence was for the adverse association with SSB intake (moderate certainty), and the weakest evidence was for the adverse association with fruit juice intake (very low certainty) and lack of association with fruit intake (very low certainty). <h3>Conclusion</h3> There is an adverse association of SSB and fruit juice intake with incident gout, which does not appear to extend to fruit intake. Further research is needed to improve our estimates. <h3>Trial registration number</h3> NCT02702375; Results.
High vaccination efficiency of low-affinity epitopes in antitumor immunotherapy
Authors: David-Alexandre Gross, Stéphanie Graff-Dubois, Paule Opolon, Sébastien Cornet, Pedro Alves, Annelise Bennaceur-Griscelli, Olivier Faure, Philippe Guillaume, Hüseyin Firat, Salem Chouaib, François A. Lemonnier, Jean Davoust, Isabelle Miconnet, Robert H. Vonderheide, Kostas Kosmatopoulos
Journal: Journal of Clinical Investigation (2004)

Most of the human tumor-associated antigens (TAAs) characterized thus far are derived from nonmutated "self"-proteins. Numerous strategies have been developed to break tolerance to TAAs, combining various forms of antigens with different vectors and adjuvants. However, no study has yet determined how to select epitopes within a given TAA to induce the highest antitumor effector response. We addressed this question by evaluating in HLA-A*0201-transgenic HHD mice the antitumor vaccination efficacy of high- and low-affinity epitopes from the naturally expressed murine telomerase reverse transcriptase (mTERT). Immunity against low-affinity epitopes was induced with heteroclitical variants. We show here that the CTL repertoire against high-affinity epitopes is partially tolerized, while that against low-affinity epitopes is composed of frequent CTLs with high avidity. The high-affinity p797 and p545 mTERT epitopes are not able to protect mice from a lethal challenge with the mTERT-expressing EL4-HHD tumor. In contrast, mice developing CTL responses against the p572 and p988 low-affinity epitopes exhibit potent antitumor immunity and no sign of autoimmune reactivity against TERT-expressing normal tissues. Our results strongly argue for new TAA epitope selection and modification strategies in antitumor immunotherapy applications in humans.
Lipid mediator profiles differ between lung compartments in asthmatic and healthy humans
Authors: Nirina Larsson, Susanna L. Lundström, Rui Pinto, Gregory Rankin, Masoumeh Karimpour, Anders Blomberg, Thomas Sandström, Jamshid Pourazar, Johan Trygg, Annelie F. Behndig, Craig E. Wheelock, Malin L. Nording
Journal: European Respiratory Journal (2013)

Oxylipins are oxidised fatty acids that can exert lipid mediator functions in inflammation, and several oxylipins derived from arachidonic acid are linked to asthma. This study quantified oxylipin profiles in different regions of the lung to obtain a broad-scale characterisation of the allergic asthmatic inflammation in relation to healthy individuals. Bronchoalveolar lavage fluid (BALF), bronchial wash fluid and endobronchial mucosal biopsies were collected from 16 healthy and 16 mildly allergic asthmatic individuals. Inflammatory cell counts, immunohistochemical staining and oxylipin profiling were performed. Univariate and multivariate statistics were employed to evaluate compartment-dependent and diagnosis-dependent oxylipin profiles in relation to other measured parameters. Multivariate modelling showed significantly different bronchial wash fluid and BALF oxylipin profiles in both groups (R 2 Y[cum]=0.822 and Q 2 [cum]=0.759). Total oxylipin concentrations and five individual oxylipins, primarily from the lipoxygenase (LOX) pathway of arachidonic and linoleic acid, were elevated in bronchial wash fluid from asthmatics compared to that from healthy controls, supported by immunohistochemical staining of 15-LOX-1 in the bronchial epithelium. No difference between the groups was found among BALF oxylipins. In conclusion, bronchial wash fluid and BALF contain distinct oxylipin profiles, which may have ramifications for the study of respiratory diseases. Specific protocols for sampling proximal and distal airways separately should be employed for lipid mediator studies.
Inhibition of Interleukin 2 Signaling and Signal Transducer and Activator of Transcription (Stat)5 Activation during T Cell Receptor–Mediated Feedback Inhibition of T Cell Expansion
Authors: In-Hong Lee, Wai Ping Li, Katherine B. Hisert, Lionel B. Ivashkiv
Journal: The Journal of Experimental Medicine (1999)

Limitation of clonal expansion of activated T cells is necessary for immune homeostasis, and is achieved by growth arrest and apoptosis. Growth arrest and apoptosis can occur passively secondary to cytokine withdrawal, or can be actively induced by religation of the T cell receptor (TCR) in previously activated proliferating T cells. TCR-induced apoptosis appears to require prior growth arrest, and is mediated by death receptors such as Fas. We tested whether TCR religation affects T cell responses to interleukin (IL)-2, a major T cell growth and survival factor. TCR ligation in activated primary human T cells blocked IL-2 induction of signal transducer and activator of transcription (STAT)5 DNA binding, phosphorylation of STAT5, Janus kinase (Jak)1, Jak3, and Akt, and kinase activity of Jak1 and Jak3. Inhibition was mediated by the mitogen-activated protein kinase kinase (MEK)–extracellular stimulus–regulated kinase (ERK) signaling pathway, similar to the mechanism of inhibition of IL-6 signaling we have described previously. TCR ligation blocked IL-2 activation of genes and cell cycle regulatory proteins, and suppressed cell proliferation and expansion. These results identify TCR-induced inhibition of IL-2 signaling as a novel mechanism that underlies antigen-mediated feedback limitation of T cell expansion, and suggest that modulation of cytokine activity by antigen receptor signals plays an important role in the regulation of lymphocyte function.
TCT-578 Vascular Responses at the Edges of the DESolve Novolimus-Eluting Bioresorbable Vascular Scaffold: Serial OCT Observations from the Pivotal, Prospective, Multicenter, DESolve NX Study
Authors: Daniel Chamie, Stefan Verheye, Joachim Schofer, Jose D. Costa, Ricardo A. Costa, Andrea Abizaid, John Yan, Vinayak Bbhat, Lynn Morrison, Sara Toyloy, Alexandre Abizaid
Journal: Journal of the American College of Cardiology (2013)
Group B streptococcal disease in UK and Irish infants younger than 90 days
Authors: Paul T Heath, Gail Balfour, Abbie M Weisner, Androulla Efstratiou, Theresa L Lamagni, Helen Tighe, Liam AF O'Connell, Mary Cafferkey, Neville Q Verlander, Angus Nicoll, A Christine McCartney
Journal: The Lancet (2004)
A sand fly salivary protein vaccine shows efficacy against vector-transmitted cutaneous leishmaniasis in nonhuman primates
Authors: Fabiano Oliveira, Edgar Rowton, Hamide Aslan, Regis Gomes, Philip A. Castrovinci, Patricia H. Alvarenga, Maha Abdeladhim, Clarissa Teixeira, Claudio Meneses, Lindsey T. Kleeman, Anderson B. Guimarães-Costa, Tobin E. Rowland, Dana Gilmore, Seydou Doumbia, Steven G. Reed, Phillip G. Lawyer, John F. Andersen, Shaden Kamhawi, Jesus G. Valenzuela
Journal: Science Translational Medicine (2015)

Immunity to sand fly salivary protein correlates to protection against cutaneous leishmaniasis in rhesus macaques.
Chronic otitis media with effusion (glue ear) and adenotonsillectomy: prospective randomised controlled study.
Authors: A R Maw
Journal: BMJ (1983)

A prospective study was conducted of the effects of adenoidectomy and adenotonsillectomy on established otitis media with effusion unresponsive to medical treatment. The operations were performed at random with a controlled no surgery group on a cohort of 103 children with the condition and the results assessed six weeks, three months, six months, nine months, and one year later. After adenoidectomy the rate of resolution of the condition increased from 39% at six weeks to 72% at one year; and after adenotonsillectomy the rate increased from 59% at six weeks to 62% at one year. In the no surgery group the rate increased from 16% at six weeks to 26% at one year. Compared with the no surgery group the effect of adenoidectomy alone at one year was highly significant (p less than 0.001), and similarly the effect of adenotonsillectomy was significant (p less than 0.01). There was, however, no increased benefit from the addition of tonsillectomy compared with adenoidectomy alone. Thus there was resolution of 36-46% of chronic effusions as a result of adenoidectomy.
Post-Camping Depression: A Lethal Possibility
Authors: DAVID J. MULLER
Journal: American Journal of Psychiatry (1971)

A two-day therapeutic camping trip with the patients, their relatives, and the staff of an adult treatment team at the Fort Logan Mental Health Center in Denver was followed by widespread depressive symptoms in many. The post-camping letdown resulted in the suicide of one patient and a suicidal gesture by another. The author suggests some possible explanations and preventive approaches.
Chemoprevention of Nonmelanoma Skin Cancer With Celecoxib: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Craig A. Elmets, Jaye L. Viner, Alice P. Pentland, Wendy Cantrell, Hui-Yi Lin, Howard Bailey, Sewon Kang, Kenneth G. Linden, Michael Heffernan, Madeleine Duvic, Ellen Richmond, Boni E. Elewski, Asad Umar, Walter Bell, Gary B. Gordon
Journal: JNCI Journal of the National Cancer Institute (2010)

BackgroundPreclinical studies indicate that the enzyme cyclooxygenase 2 plays an important role in ultraviolet-induced skin cancers. We evaluated the efficacy and safety of celecoxib, a cyclooxygenase 2 inhibitor, as a chemopreventive agent for actinic keratoses, the premalignant precursor of nonmelanoma skin cancers, and for nonmelanoma skin cancers, including cutaneous squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs).
The development of autoimmunity in C57BL/6 lpr mice correlates with the disappearance of natural killer type 1-positive cells: evidence for their suppressive action on bone marrow stem cell proliferation, B cell immunoglobulin secretion, and autoimmune symptoms.
Authors: K Takeda, G Dennert
Journal: The Journal of Experimental Medicine (1993)

F1 hybrid mice are able to acutely reject parental marrow grafts, a phenomenon that is due to natural killer type 1-positive (NK1+) cells. Circumstantial evidence had suggested that the antigenic determinants recognized by these cells are self-antigens, leading to the hypothesis that the physiological role of NK1+ cells is a downregulatory or suppressive function on bone marrow stem cell proliferation and lymphocyte function. In analyzing this hypothesis it is shown here that in young mice there is a temporal correlation between appearance of NK1+ cells in the spleen and the ability to reject allogeneic marrow or to suppress endogenous stem cell proliferation. The reverse situation exists in mice expressing the homozygous lpr gene. Whereas in young mice cells with NK1+ phenotype are demonstrable, these cells disappear with age, i.e., at the time autoimmunity develops. Concomitant with the disappearance of NK1+ cells, the ability to reject marrow grafts and to control endogenous stem cell proliferation also vanishes. The suggestion that the development of autoimmunity is causally related to the disappearance of NK1+ cells is supported by experiments in which NK1+ cells were either eliminated by antibody injection or increased by adoptively transferring cell populations enriched for NK1+ cells into lpr mice. It is shown that removal of cells enhances autoimmunity, whereas injection of NK1+ cells delays the onset of autoimmunity. In vitro assays are presented that demonstrate that suppression of autoantibody-secreting B cells is due to two NK1+ cell populations, one that expresses CD3 and causes specific suppression and one that lacks CD3 and causes nonspecific suppression.
Clinical and pathological study of asymptomatic HBsAg carriers in Chile.
Authors: M Velasco, M Gonzalez-Ceron, C de la Fuente, A Ruiz, S Donoso, R Katz
Journal: Gut (1978)

A clinical, biochemical, and pathological study was performed in 38 chronic HBsAg carriers. The study group is a part of 393 carriers found among 117 705 voluntary blood donors at the National Blood Bank, Hospital del Salvador, Santiago, Chile. None of the 38 carriers had a past history of illicit drug abuse, hepatitis, or work involving a high risk of hepatitis B virus infection. Ten individuals had a normal liver biopsy, 17 reactive non-specific hepatitis, one fatty changes, four chr onic persistent hepatitis, one aggressive hepatitis, two post-necrotic cirrhosis, and three alcoholic cirrhosis. There was not a close correlation between liver function test and liver histology. The most significant laboratory finding was the postivity of alpha fetoprotein in two cases. During the follow-up the two alpha fetoprotein patients presented a hepatocarcinoma 12 and 14 months after admission to the study.
Overview of <i>Pyridine Nucleotides</i> Review Series
Authors: Michinari Nakamura, Aruni Bhatnagar, Junichi Sadoshima
Journal: Circulation Research (2012)

Pyridine nucleotides are abundant soluble coenzymes and they undergo reversible oxidation and reduction in several biological electron-transfer reactions. They are comprised of two mononucleotides, adenosine monophosphate and nicotinamide mononucleotide, and are present as oxidized and reduced nicotinamide adenine dinucleotides in their unphosphorylated (NAD(+) and NADH) and phosphorylated (NADP(+) and NADPH) forms. In the past, pyridine nucleotides were considered to be primarily electron-shuttling agents involved in supporting the activity of enzymes that catalyze oxidation-reduction reactions. However, it has recently been demonstrated that pyridine nucleotides and the balance between the oxidized and reduced forms play a wide variety of pivotal roles in cellular functions as important interfaces, beyond their coenzymatic activity. These include maintenance of redox status, cell survival and death, ion channel regulation, and cell signaling under normal and pathological conditions. Furthermore, targeting pyridine nucleotides could potentially provide therapeutically useful avenues for treating cardiovascular diseases. This review series will highlight the functional significance of pyridine nucleotides and underscore their physiological role in cardiovascular function and their clinical relevance to cardiovascular medicine.
The transcription factor interferon regulatory factor-1 is essential for natural killer cell function in vivo.
Authors: G S Duncan, H W Mittrücker, D Kägi, T Matsuyama, T W Mak
Journal: The Journal of Experimental Medicine (1996)

The activation of natural killer (NK) cells, cytotoxic lymphocytes capable of major histocompatibility complex (MHC)-unrestricted killing and early antiviral defense, is temporally related to the increased interferon (IFN)-alpha/beta production that is seen in the viral infection of mice. Type I IFN (IFN-alpha/beta) are expressed in many cell types early after primary viral infection and have been shown to mediate resistance against a variety of viruses. In this study, the role of the transcriptional activator IFN regulatory factor-1 (IRF-1) in murine NK cell activity was assessed. IRF-1-deficient mice displayed a normal frequency of NK marker-positive cells, but exhibited greatly reduced NK cell-mediated cytotoxicity after both virus infection and stimulation with the IFN inducer polyinosinic:polycytidilic acid in vivo. In vitro, cytolytic activity in IRF-1-deficient NK cells remained defective after stimulation with IFN-beta, IL-2, and IL-12. IRF-1-deficient mice were unable to eliminate syngeneic MHC class I-negative tumor cells in vivo, and had a reduced ability to reject parental semi-allogeneic donor cells from the circulation. Thus, IRF-1 is essential for the induction of NK cell-mediated cytotoxicity and for the in vivo effector functions that are mediated by this activity.
Bepreve (Bepotastine Besilate Ophthalmic Solution) 1.5% Improves Morning (AM) Ocular Redness Scores in a Placebo-Controlled Environmental Study of Seasonal Allergic Rhinoconjunctivitis (SAR)
Authors: J.I. Williams, J.A. Gow, M. Munoz, T. McNamara
Journal: Journal of Allergy and Clinical Immunology (2012)