tbuckley/cabot-search huggingface dataset:
Effect of Luminal Sodium Concentration on Bicarbonate Absorption in Rat Jejunum
Authors: Kenneth A. Hubel
Journal: Journal of Clinical Investigation (1973)

An exchange of Na(+) for H(+) has been proposed to explain why jejunal Na(+) absorption is influenced by luminal concentrations of H(+) and HCO(3) (-). We studied the influence of luminal Na(+) concentration on net HCO(3) (-) absorption by perfusing rat jejunum in vivo. When Na(+) was omitted from the perfusion fluid, HCO(3) (-) absorption diminished by a fixed amount over a range of initial HCO(3) (-) concentrations of 15 to 80 mM. This change was not caused by alterations in transmural PD or direction of water movement. Because the rate of HCO(3) (-) absorption decreased as the luminal HCO(3) (-) concentration lessened, Na(+)-dependent HCO(3) (-) absorption accounted for an increasing percent of total absorption as the luminal concentration of HCO(3) (-) diminished. The effect of Na(+) on HCO(3) (-) absorption is mediated, at least in part, by H(+) secretion, because luminal CO(2) production (manifested by luminal P(CO2)) dimished as HCO(3) (-) absorption decreased. The changes in P(CO2) are caused by reaction of H(+) with HCO(3) (-) in the luminal fluid because luminal P(CO2) is augmented by the presence of HCO(3) (-) and is diminished by addition of phosphate or Tris buffer. Whether all H(+) secretion requires luminal Na(+) cannot be determined with these experimental techniques because mucosal permeability to Na(+) and the unstirred layer make it impossible to eliminate Na(+) ions from the luminal cell surface. The nature of the mechanism for HCO(3) (-) transport that is not sodium dependent remains to be determined.
Pharmacotherapy for Obesity — Promise and Uncertainty
Authors: Susan Z. Yanovski
Journal: New England Journal of Medicine (2005)

In 2005, a majority of adult Americans are overweight or obese,1 putting millions of them at increased risk for serious medical conditions, including cardiovascular disease, type 2 diabetes mellitus, and certain forms of cancer. In obesity, a weight loss of 5 to 10 percent can significantly improve risk factors for obesity-related diseases2 and delay or prevent type 2 diabetes in persons at high risk.3 Behavioral treatments can result in a weight loss sufficient to improve health for many patients, but often the weight is regained over time.4 Although for many people a reduction in weight is difficult to achieve, maintaining . . .
Apolipoprotein E and Coronary Disease: A Puzzling Paradox
Authors: Muredach Reilly, Daniel J Rader
Journal: PLoS Medicine (2006)

Apolipoprotein E (apoE) has effects on lipoprotein metabolism and the vasculature that have long been considered to be anti-atherogenic [ 1]. In the plasma, apoE is found on the surface of triglyceride-rich lipoproteins, such as very low density lipoproteins (VLDL) and remnant particles. ApoE is also found on high density lipoproteins (HDL) and as such may serve distinct functions depending on its specific lipoprotein association.
Antimitochondrial Antibodies in Jaundice Following Drug Administration
Authors: Moravia Rodriguez
Journal: JAMA (1969)

Antimitochondrial antibodies were detected by fluorescent antibody technique in seven of nine sera from patients with jaundice after halothane anesthesia, and from four of seven patients with jaundice after therapy chlorpromazine. They were not observed in jaundized patients treated with other drugs (methyldopa, aminosalicylic acid, chlorpropamide, perphenazine), in patients in whom jaundice did not develop after receiving halothane or chlorpromazine, or in patients with viral hepatitis. The presence of antibodies may help differentiate between viral hepatitis and some forms of jaundice after drug administration.
Post-pill amenorrhoea.
Authors: K W Hancock, J S Scott
Journal: BMJ (1978)

induction of labour (8 7 %) and to their low incidence of caesarean section (3 8 ,').Of equal importance is that, in addition to one perinatal death from meconium aspiration at 41 weeks, they record five late fetal deaths before the onset of labour.Details of these deaths are not presented, but it seems likely that they may represent the stillbirths associa- ted with late placental failure which are
Ectopic Secretion of Calcitonin by Oat-Cell Carcinoma
Authors: Omega L. Silva, Kenneth L. Becker, Aron Primack, John Doppman, Richard H. Snider
Journal: New England Journal of Medicine (1974)

SEVERAL humoral substances are ectopically produced by cancer tissue.1 2 3 Bronchogenic cancer —in particular, oat-cell carcinoma of the lung — appears to be "multipotential" in this regard. Calcitonin, the hypocalcemic hormone normally produced by the C cells of the thyroid, may now be added to the list of hormones that may be elaborated by this tumor.We have developed a radioimmunoassay for human calcitonin,4 which we have used in a prospective study of normocalcemic patients with bronchogenic carcinoma of several cell types. More than 50 per cent of the patients studied had plasma calcitonin levels above 400 pg per milliliter. We . . .
Homeless in DC
Authors: Samuel Wallace Bender
Journal: JAMA (2011)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Hormone-associated cancer: mechanistic similarities between human breast cancer and estrogen-induced kidney carcinogenesis in hamsters.
Authors: J G Liehr
Journal: Environmental Health Perspectives (1997)

Estrogens are risk factors for human breast cancer and induce kidney tumors in Syrian hamsters. Mechanistic features of the estrogen-induced hamster kidney tumor model have been compared with corresponding aspects of human breast cancer to gain insight into the mechanism of human mammary oncogenesis. Shared characteristics point to a mechanism of metabolic activation of steroidal estrogens to 4-hydroxylated catechol metabolites that may undergo metabolic redox cycling, a mechanism of generation of reactive free radicals. Tumors may arise in cells genetically altered by various types of estrogen-induced DNA damage. At the same time, these altered cells may respond to estrogen receptor-mediated stimuli in support of cell transformation and growth.
Selective serotonin reuptake inhibitors (SSRIs) and routine specialist care with and without cognitive behaviour therapy in adolescents with major depression: randomised controlled trial
Authors: Ian Goodyer, Bernadka Dubicka, Paul Wilkinson, Raphael Kelvin, Chris Roberts, Sarah Byford, Siobhan Breen, Claire Ford, Barbara Barrett, Alison Leech, Justine Rothwell, Lydia White, Richard Harrington
Journal: BMJ (2007)

<b>Objective</b> To determine whether a combination of a selective serotonin reuptake inhibitor (SSRIs) and cognitive behaviour therapy (CBT) together with clinical care is more effective in the short term than an SSRI and clinical care alone in adolescents with moderate to severe major depression. <b>Design</b> Pragmatic randomised controlled superiority trial. <b>Setting</b> 6 outpatient clinics in Manchester and Cambridge. <b>Participants</b> 208 adolescents, aged 11-17, with moderate to severe major or probable major depression who had not responded to a brief initial intervention. Adolescents with suicidality, depressive psychosis, or conduct disorder were included. <b>Interventions</b> 103 adolescents received an SSRI and routine care; 105 received an SSRI, routine care, and CBT. The trial lasted 12 weeks, followed by a 16 week maintenance phase. <b>Main outcome measures</b> Change in score on the Health of the Nation outcome scales for children and adolescents (primary outcome) from baseline with 12 weeks as the primary and 28 weeks as the follow-up end point. Secondary measures were change in scores on the mood and feelings questionnaire, the revised children9s depression rating scale, the children9s global assessment scale, and the clinical global impression improvement scale. <b>Results</b> At 12 weeks the treatment effect for the primary outcome was −0.64 (95% confidence interval −2.54 to 1.26, P=0.50). In a longitudinal analysis, there was no difference in effectiveness of treatment for the primary (average treatment effect 0.001, −1.52 to 1.52, P=0.99) or secondary outcome measures. On average there was a decrease in suicidal thoughts and self harm. There was no evidence of a protective effect of cognitive behaviour therapy on suicidal thinking or action. By 28 weeks, 57% were much or very much improved with 20% remaining unimproved. <b>Conclusions</b> For adolescents with moderate to severe major depression there is no evidence that the combination of CBT plus an SSRI in the presence of routine clinical care contributes to an improved outcome by 28 weeks compared with the provision of routine clinical care plus an SSRI alone. <b>Trial registration</b> Current Controlled Trials ISRCNT 83809224.
Phosphodiesterase 11A (PDE11A) and Genetic Predisposition to Adrenocortical Tumors
Authors: Rossella Libé, Amato Fratticci, Joel Coste, Frédérique Tissier, Anelia Horvath, Bruno Ragazzon, Fernande Rene-Corail, Lionel Groussin, Xavier Bertagna, Marie Laure Raffin-Sanson, Constantine A. Stratakis, Jérome Bertherat
Journal: Clinical Cancer Research (2008)

Abstract Purpose: We have reported previously nonsense inactivating mutations of the phosphodiesterase 11A (PDE11A) gene in patients with micronodular adrenocortical hyperplasia and Cushing syndrome. The aim of this study is to investigate the presence of somatic or germ-line PDE11A mutations in various types of adrenocortical tumors: ACTH-independent macronodular adrenocortical hyperplasia (AIMAH), adrenocortical adenoma (ACA), and adrenocortical cancer (ACC). Experimental Design: PDE11A was sequenced in 117 adrenocortical tumors and 192 controls subjects; immunohistochemistry for PDE11A and tumor cyclic AMP levels were studied in a subgroup of adrenocortical tumors. Results: One PDE11A inactivating mutation (R307X) was found in one ACA, 22 germ-line missense variants (18.8%) were found in adrenocortical tumors, and only 11 missense variants (5.7%) were found in controls. By comparing the common mutations, a higher frequency of mutations in adrenocortical tumors than in age/sex-matched controls were observed [16% versus 10% in ACC, 19% versus 10% in ACA, and 24% versus 9% in AIMAH; odds ratio (OR), 3.53; P = 0.05]. Somatic DNA from adrenocortical tumors with missense variants showed a wild-type allelic loss. A significant difference between ACC and controls was observed for a polymorphism in exon 6 (E421E; OR, 2.1; P = 0.03) and three associated polymorphisms located in intron 10-exon 11-intron 11 (OR, 0.5; P = 0.01). In AIMAH/ACA, cyclic AMP levels were higher than in normal adrenals and decreased PDE11A immunostaining was present in adrenocortical tumors with PDE11A variants. Conclusions: The present investigation of a large cohort of adrenocortical tumors suggests that PDE11A sequence defects predispose to a variety of lesions (beyond micronodular adrenocortical hyperplasia) and may contribute to the development of these tumors in the general population.
Rheumatoid arthritis is milder in the new millennium: health status in patients with rheumatoid arthritis 1994-2004
Authors: T Uhlig, T Heiberg, P Mowinckel, T K Kvien
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Aims</h3> This systematic review aims to understand the challenges faced by adolescents and young adults (11-25 years) with allergic diseases, including asthma. <h3>Methods</h3> A search strategy was constructed using Cochrane Database of Systematic Reviews, MEDLINE, Embase and Psychinfo. Databases were searched to February 10, 2019. Quality assessments and data extraction were undertaken independently by two reviewers. <h3>Results</h3> 108 papers describing 106 studies were included. Most were from USA (n=50), Netherlands (n=12), Sweden (n=11) and UK (n=11). Most focused on asthma (n=69) or food allergy (n=19). They were qualitative, cross-sectional or longitudinal quantitative studies. There were five themes.<sup>1</sup> Quality of life, as a measure of patients' experience of life. Factors associated with impaired quality of life: symptomatic disease, impaired psychological health, onset in adolescence, poor adherence, female sex and multiple allergies. Protective factors were exercise and increasing age.<sup>2</sup> Psychological factors. Social anxiety has been associated with asthma and food allergy; it may inhibit patients from using medication in front of peers. Depression has also be associated with asthma and food allergy while suicidal ideation has been associated with eczema. Emotional support from family and friends has been found to be protective for asthma control.<sup>3</sup> Adherence. Factors associated with poor adherence are older age; barriers to using medication such as lack of time, forgetfulness, cost, competing demand and accessibility, over reliance on short-acting rescue medication or poor knowledge; lack of perception of symptoms; and lack of personal responsibility. Factors associated with good adherence were routine, good self-efficacy, simple medication regimes and good knowledge about their disease. Patients who need to carry self-injectable adrenaline seem to be particularly non-adherent; the burden of these and incorrect knowledge around risks leading to poor decision making.<sup>4</sup> Self-management. This extended from the previous theme and involved a series of barriers and corresponding facilitators.<sup>5</sup> Supportive relationships. Key ones were identified as families, peers, friend and schools and healthcare professionals. <h3>Conclusion</h3> The current evidence base to support the planned European guidelines for managing allergic disease in this age group is weak. Large longitudinal cohort and interventional studies are required to strength the evidence base.
Type IIB von Willebrand's Disease: Unusual Response to Cryoprecipitate Infusion
Authors: RONALD S. WEINGER
Journal: Annals of Internal Medicine (1981)

A 16-year-old boy had IIB von Willebrand's disease. The disorder is characterized by prolonged bleeding times; normal plasma levels of factor VIII-coagulant activity, factor VIII-ristocetin cofactor activity, and factor VIII-related antigen; abnormal (anodal) mobility of plasma factor VIII-related antigen on two-dimensional crossed Immunoelectrophoresis; and enhanced binding of plasma factor VIII-related antigen to normal platelets in the presence of ristocetin. These variables were measured at time periods after an infusion of normal cryoprecipitate into the patient. The electrophoretic mobility of his plasma factor VIII-related antigen was normal 15 minutes after the infusion but became abnormal (anodal) by 4 hours. His bleeding times were normal after 24 hours and did not correlate with plasma levels of factor VIII-coagulant activity, factor VIII-ristocetin cofactor, factor VIII-related antigen, or the electrophoretic mobility of his plasma factor VIII-related antigen. These results imply that the abnormal factor VIII/von Willebrand factor multimers in the plasma of these patients can associate with normal factor VIII/von Willebrand factor multimers and delay the deposition of the normal multimers into subendothelial surfaces. This may require cryoprecipitate infusions 24 hours before elective surgical procedures.
Differential Expression of CXCR4 Is Associated with the Metastatic Potential of Human Non–Small Cell Lung Cancer Cells
Authors: Liping Su, Jinping Zhang, Huanbin Xu, Ying Wang, Yiwei Chu, Ruizi Liu, Sidong Xiong
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To evaluate the relation between CXCR4 expression and the presence of metastatic disease in human non–small cell lung cancer (NSCLC) patients and investigate whether modulation of CXCR4 expression could serve as a potential pathway in preventing metastasis of NSCLC. Experimental Design: CXCR4 expression in 36 patients with NSCLC and 10 normal lung tissues was detected by real-time PCR and immunohistochemistry. CXCR4 expression in two human NSCLC clones (95C and 95D) with different metastatic potential was determined by real-time PCR and flow cytometry. 95C and 95D cells were transfected with the plasmid DNA containing CXCR4 coding gene or CXCR4 antisense nucleotide fragment, respectively, and the effects on in vitro cell migration, invasion, and adhesion and in vivo metastasis were measured. Results: Up-regulated expression of CXCR4 was detected in 34 tumors, which were further divided into 17 high expression cancers and 17 low expression cancers by their staining intensities. High CXCR4 tumors (13 of 17) were more prone to clinical metastasis in comparison with low expression tumors. CXCR4 was differentially expressed in 95C and 95D cells with low or high metastatic potential, and the surface expression of CXCR4 were 50% up-regulated or down-regulated following the stable transfection. The metastatic potential of NSCLC in vitro, such as migration, invasion, and adhesion, were significantly enhanced or impaired. In addition, neutralizing the interactions of stromal cell–derived factor-1/CXCR4 in vitro with CXCR4-specific antibodies inhibited the CXCR4-dependent migration, invasion, and adhesion. Furthermore, s.c. inoculation of lung cancer cells with low expression of CXCR4 in nude mice showed 0- to 2-fold decrease in lung metastatic foci than that with high expression of CXCR4. Conclusions: Differential expression of CXCR4 is associated with the metastatic potential of human NSCLC, raising the possibility that blockade of CXCR4/stromal cell–derived factor-1 interaction may lead the way to design novel therapeutic tools for the treatment of metastatic NSCLC patients.
Abstract 3806: Progressive biallelic loss of TP53 is associated with progression of pleuropulmonary blastoma initiated by germline loss and somatic mutation of DICER1.
Authors: Trevor J. Pugh, Weiying Yu, Jiandong Yang, Lauren Ambrogio, Scott L. Carter, Adam Kiezun, Aaron McKenna, Petros Giannikopoulos, Gad Getz, Yoav Messinger, Matthew Meyerson, D. Ashley Hill
Journal: Cancer Research (2013)

Abstract Pleuropulmonary blastoma (PPB) is a rare, aggressive childhood cancer arising from lung mesenchymal cells. In early stages, these cells reside in the walls of epithelial-lined cysts and may remain dormant or progress to thickened cysts and then highly malignant masses over several years. Familial germline loss-of-function DICER1 variants have been described, although carriers may not be affected. Therefore, we sought to uncover additional genetic events underlying tumor development through whole exome sequencing of 15 tumor/normal pairs. In addition to known loss-of-function germline variants found throughout DICER1, this analysis identified somatic missense mutations clustered in the DICER1 RNase IIIb domain in nearly every case. While the somatic mutations impact novel amino acid residues, expression analysis demonstrated depletion of 5p-derived miRNAs similar to that described in other DICER1-mutant tumors. While mutation rates were relatively high compared to other pediatric solid tumors, most mutations, except those in DICER1 and TP53, appeared to be subclonal. Early stage tumors (PPB Type II) had predominantly single-copy deletion of TP53 whereas late stage tumors (PPB Type III) had secondary TP53 mutations. Several late stage tumors also had activating mutations in RAS pathway members, including NRAS and BRAF. Therefore, compound DICER1 loss appears to be initiating and synergistic with incremental loss of TP53 and acquisition of additional driver mutations. We subsequently characterized this molecular pattern using deep sequencing and immunohistochemistry in an extension cohort of 45 additional tumors. This step-wise series of germline and somatic alterations illustrates a genetic mechanism consistent with the progressive nature of pleuropulmonary blastoma. Citation Format: Trevor J. Pugh, Weiying Yu, Jiandong Yang, Lauren Ambrogio, Scott L. Carter, Adam Kiezun, Aaron McKenna, Petros Giannikopoulos, Gad Getz, Yoav Messinger, Matthew Meyerson, D. Ashley Hill. Progressive biallelic loss of TP53 is associated with progression of pleuropulmonary blastoma initiated by germline loss and somatic mutation of DICER1. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3806. doi:10.1158/1538-7445.AM2013-3806
Environmental tobacco smoke, parental atopy, and childhood asthma.
Authors: J J Jaakkola, P Nafstad, P Magnus
Journal: Environmental Health Perspectives (2001)

We hypothesized that the joint effect of genetic propensity to asthma and exposure to environmental tobacco smoke on the risk of childhood asthma is greater than expected on the basis of their independent effects. We performed a population-based 4-year cohort study of 2,531 children born in Oslo, Norway. We collected information on the child's health and environmental exposures at birth and when the child was 6, 12, 18, and 24 months and 4 years of age. The outcomes of interest were bronchial obstruction during the first 2 years and asthma at the age of 4 years. Parental atopy was defined as a history of maternal or paternal asthma or hay fever. Exposure to environmental tobacco smoke was defined on the basis of questionnaire information on household smokers at birth. In logistic regression analysis adjusting for confounding, parental atopy alone increased the risk of bronchial obstruction [odds ratio 1.62; 95% confidence interval (CI) 1.10-2.40] and asthma (1.66; 95% CI, 1.08-2.54). In children without parental atopy, there was little effect of exposure to environmental tobacco smoke on bronchial obstruction (1.29; 95% CI, 0.88-1.89) and asthma (0.84; 95% CI, 0.53-1.34). The presence of parental atopy and exposure had a substantial effect both on bronchial obstruction (2.88; 95% CI, 1.91-4.32) and asthma (2.68; 95% CI, 1.70-4.22). The results are consistent with the hypothesized joint effect of parental atopy and exposure to environmental tobacco smoke. This phenomenon--denoted as effect modification of environmental exposure by genetic constitution, or gene by environment interaction--suggests that some genetic markers could indicate susceptibility to environmental factors.
How cortical neurons help us see: visual recognition in the human brain
Authors: Julie Blumberg, Gabriel Kreiman
Journal: Journal of Clinical Investigation (2010)

Through a series of complex transformations, the pixel-like input to the retina is converted into rich visual perceptions that constitute an integral part of visual recognition. Multiple visual problems arise due to damage or developmental abnormalities in the cortex of the brain. Here, we provide an overview of how visual information is processed along the ventral visual cortex in the human brain. We discuss how neurophysiological recordings in macaque monkeys and in humans can help us understand the computations performed by visual cortex.