tbuckley/cabot-search huggingface dataset:
Common variants in FCER1A influence total serum IgE levels from cord blood up to six years of life
Authors: C.‐M. Chen, S. Weidinger, N. Klopp, S. Sausenthaler, W. Bischof, O. Herbarth, M. Bauer, M. Borte, B. Schaaf, I. Lehmann, H. Behrendt, U. Krämer, D. Berdel, A. Von Berg, C. P. Bauer, S. Koletzko, T. Illig, H.‐E. Wichmann, J. Heinrich
Journal: Allergy (2009)

In a recent genome wide scan, a functional promoter variant (rs2251746) in the gene encoding the alpha chain of the high affinity receptor for immunoglobulin E (IgE) (FCER1A) was identified as major determinant of serum IgE levels.The aim of this study was to investigate the role of rs2251746 on total IgE levels measured at different stages of life from birth (cord blood) up to the age of 6 and to evaluate its interaction with the environmental influences in two German birth cohorts.Data from two German birth cohorts were analysed (n = 1043 for the LISA cohort and n = 1842 for the GINI cohort). In the studies, total serum IgE was measured from cord blood, and blood samples taken at the age of 2/3 and 6 years. In a subgroup of the LISA study, house dust samples were collected at age of 3 months and the amount of endotoxin was determined. Random effect models were used to analyse the longitudinal health outcomes.In the two cohorts, the heterozygote and the rare homozygote of rs2251746 was consistently associated with lower total IgE levels from birth up to the age of 6 years with an allele-dose effect (P < 0.02 for blood samples taken at each time point in both cohorts). No interaction between the two FCER1A encoding gene and environmental exposures including endotoxin, worm infestation and day care centre attendance during early childhood were observed.Common variants in FCER1A strongly influence basal IgE production independently from environmental stimuli. These effects can be observed already in cord blood pointing to altered gene expression in foetus.
Abstract P3-10-18: Early Detection of Recurrent Breast Cancer Using Metabolite Profiling
Authors: VM Asiago, LZ Alverado, N Shanaiah, NG Gowda, K Owusu-Sarfo, R Ballas, D Raftery
Journal: Cancer Research (2010)

Abstract Background: The growing field of metabolite profiling (or metabolomics) focuses on the quantitative detection of multiple small molecules in biological systems that result from pathophysiological stimuli. As is the case for early detection of primary breast cancer, it is anticipated that early diagnosis of breast cancer recurrence will not only improve survival but also help clinicians determine the best therapeutic strategies for patients by avoiding under or over treatment. We report on the development of an early test for recurrent breast cancer using metabolite profiling methods. Methods: We applied a combination of nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (2D GC-MS) to analyze the metabolite profiles of 257 serial serum samples from breast cancer patients consisting 116 samples from breast cancer recurrence and 141 samples from breast cancer patients with no evidence of disease (NED). NMR and GC-MS data were analyzed by combining advanced univariate and multivariate statistical methods and comparison of individual spectral features between patients with and without recurrent breast cancer. Results: From multivariate analysis of hundreds of spectral features, ten metabolite markers (7 from NMR and 3 from GC-MS) were targeted to build logistic regression model, which yielded a prediction model with a high accuracy (AUROC &amp;gt;0.89 using 5 fold cross validation) with a sensitivity of 86% and specificity of 89%. When the model was tested using leave one patient cross validation it yielded a sensitivity of 75% and a specificity of 83% (AUROC &amp;gt;0.88). In addition, strikingly, over 55% of the patients could be correctly predicted to have recurrence as early as 13 months before the recurrence was actually diagnosed clinically, representing a large improvement over the current diagnostic assay CA 27.29. A second statistical approach using independent training and testing sets yielded very similar results. To the best of our knowledge, this is the first study to develop and validate a prediction model for early detection of recurrent breast cancer based on the metabolic profiling. The combination of complementary NMR and MS analytical methodologies is particularly useful for building accurate profiles. Conclusion: Metabolite profiling methods provide a powerful approach for the development of diagnostic tests for monitoring breast cancer patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-18.
Protein kinase A and C site-specific phosphorylations of LAP (NF-IL6) modulate its binding affinity to DNA recognition elements.
Authors: C Trautwein, P van der Geer, M Karin, T Hunter, M Chojkier
Journal: Journal of Clinical Investigation (1994)

LAP (NF-IL6 or C/EBP beta), is a liver transcriptional activator protein that confers liver-specific gene expression. Because LAP has a characteristic phosphoacceptor sequence for cAMP-dependent protein kinase A (PKA), we tested if in vitro phosphorylation of LAP by PKA modulates its interaction with specific DNA sequences. The major PKA phosphorylation site of LAP was identified as Ser105, which is a predicted PKA site. As expected, this PKA phosphorylation site disappears after mutation of Ser105 to Ala. Kinetic studies with LAP and LAP Asp105 (which mimics a phosphoserine residue) demonstrated that phosphorylation of Ser105 itself has no effect on DNA binding. Phosphorylation of other sites by PKA, identified in the region between Ser173 and Ser223 and at Ser240, by analysis of truncated and mutated LAP peptides, resulted in an inhibition of DNA binding. LAP was also phosphorylated by purified protein kinase C in vitro, and the major phosphoacceptor was shown to be Ser240 within the DNA-binding domain of LAP. Phosphorylation of LAP at this residue or introduction of a Ser240 to Asp mutation resulted in marked decrease in its binding to DNA. These results suggest that site-specific phosphorylations of LAP modulate transactivation of its target genes.
Heat shock protein 27 expression in human proximal tubule cells exposed to lethal and sublethal concentrations of CdCl2.
Authors: S Somji, D A Sens, S H Garrett, M A Sens, J H Todd
Journal: Environmental Health Perspectives (1999)

The expression of hsp 27 mRNA and protein was determined in cultured human proximal tubule (HPT) cells exposed to lethal and sublethal concentrations of Cd2+ under both acute and extended conditions. Initial procedures demonstrated that HPT cells display the classic stress response following physical and chemical stress. Heat stress (42.5 degrees C for 1 hr) caused an increase in both hsp 27 mRNA and protein as well as a shift in the protein to a more phosphorylated state. Results were similar when the cells were subjected to chemical stress (exposure to 100 microM sodium arsenite for 4 hr). Acute exposure to 53 microM CdCl2 for 4 hr also resulted in an increase in hsp 27 mRNA and protein and a shift to the more phosphorylated protein isoform. Extended Cd2+ exposure involved continuous treatment with Cd2+ at both lethal and sublethal levels over a 16-day time course. The results of this treatment showed that chronic exposure to Cd2+ failed to increase either hsp 27 mRNA or protein expression in HPT cells, even at lethal Cd2+ concentrations. In fact, hsp 27 protein levels decreased as compared to controls at both lethal and sub-lethal exposure to Cd2+. These findings imply that hsp 27 expression in human proximal tubule cells may have two distinct modes depending on the nature (acute vs. chronic) of the stress.
Atrial Echo Beats in the Human Heart Elicited by Induced Atrial Premature Beats
Authors: R. M. SCHUILENBURG, D. DURRER
Journal: Circulation (1968)

In a patient with atrial septal defect and incomplete right bundle-branch block atrial echo beats were observed after atrial premature beats, induced with a gradually decreasing delay during regular driving of the atrium. The time relations of these atrial echo beats could be accurately defined. Considerable prolongation of the atrioventricular (A-V) conduction of the premature atrial response was found to be a necessary condition for the occurrence of atrial reciprocation, which was restricted to small and very circumscript delay ranges. Three types of atrial echo responses could be discerned. The concept of a dual A-V conduction system was not sufficient to explain the genesis of these three types. The assumption of a third pathway in the upper part of the A-V node was needed. Arguments in favor of a longitudinal dissociation of one of the two pathways postulated in the concept of dual A-V transmission were given.
Ruptured Peptic Ulcer
Authors: Arnold H. Kadish
Journal: JAMA (1961)

<h3>To the Editor:—</h3> In the paper, "Ruptured Peptic Ulcer During Triamcinolone Therapy," inThe JournalJune 25, page 900, the authors neglected to mention that ACTH can be an extremely important cause of ruptured peptic ulcer, especially while the patient is receiving large amounts of aspirin. Because of this, the title of the case report seems to be a misnomer. Acute perforations are not uncommon following such a combination of therapy, and frequent use of non-absorbable antacids should be the rule.
The Synthesis of Biologically Active Peptides and Proteins
Authors: Robert Bruce Merrifield
Journal: JAMA (1969)

The proteins are key components of all living organisms, and their fundamental role in biology cannot be overestimated. These very large and extremely complex substances are major constituents of blood, muscle, skin, bone, nerve, and, in fact, of every tissue and organ of the body. All of the enzymes that catalyze biochemical reactions and many of the hormones that regulate them are proteins. If we are to understand, and eventually control, the events that occur in the body, we must first understand the composition, structure, and function of the individual proteins. One way is to study proteins isolated from natural sources. Another way is to make the proteins in the laboratory and to study the synthetic material. Although the total chemical synthesis of a protein was out of the question a decade ago, it was not unreasonable to begin thinking of the day when a synthesis might be achieved and
Abstract 665: Targeting the pro-apoptotic protein BIM by dexamethasone combined with a MEK inhibitor PD184352 enhances the lethality in acute lymphoblastic leukemia
Authors: Nastaran Heidari, Amanda Richardson, Mark Hicks, Keneshia Turner, Hisashi Harada
Journal: Cancer Research (2010)

Abstract Glucocorticoids (GC) represent common components of many chemotherapeutic regimens for lymphoid malignancies including acute lymphoblastic leukemia (ALL). Although the effects of GC on lymphocytes have been scrutinized for many years, the molecular mechanisms of sensitivity and resistance need to be elucidated. Since GC-resistant leukemia and myeloma are often associated with GC receptor defects, bypassing the receptor by targeting downstream molecules may develop new therapeutic strategies. We and others have previously shown that BIM (BCL-2 Interacting Mediator of cell death), a pro-apoptotic BCL-2 family protein, is up-regulated by dexamethasone (Dex) treatment in ALL cells and plays an essential role in Dex-induced apoptosis. Furthermore, BIM is inactivated by extracellular signal-regulated kinase (ERK)-mediated phosphorylation by survival/growth factors. We therefore hypothesized that co-treatment with Dex and MEK/ERK inhibitors promote apoptosis in ALL cells through BIM up-regulation and activation, resulting in cell death. We have recently demonstrated that MEK inhibitors synergistically promote Dex lethality in a variety of ALL cell lines, in which BIM is a critical molecule in cell death (Rambal et al., Leukemia 23, 1744-1754, 2009). In the present study, we examined the therapeutic potential of co-treatment of Dex and MEK inhibitor PD184352 in vivo by severe combined immunodeficiency (SCID) mouse xenograft models of ALL. Minimum doses of Dex (8 mg/kg/day) and PD184352 (50 mg/kg/day) treatment caused BIM up-regulation and ERK dephosphorylation in xenograft tumor samples, respectively. Co-treatment of Dex and PD184352 resulted in an increase of apoptosis determined by caspase-3 cleavage and a significant decrease in size of the tumors. These data show that MEK/ERK inhibition enhances the anti-tumor activity of Dex in vivo. Our study provides a rational foundation for future attempts to improve the effect of GC with clinically relevant pharmacologic MEK inhibitors in the treatment of ALL and possibly other hematological malignancies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 665.
Plasma Activity and Insertion/Deletion Polymorphism of Angiotensin I–Converting Enzyme
Authors: Flavio Ribichini, Giuseppe Steffenino, Antonio Dellavalle, Giuseppe Matullo, Elena Colajanni, Terenzio Camilla, Antonello Vado, Gabriella Benetton, Eugenio Uslenghi, Alberto Piazza
Journal: Circulation (1998)

Background —Tissue proliferation is almost invariably observed in recurrent lesions within stents, and ACE, a factor of smooth muscle cell proliferation, may play an important role. Plasma ACE level is largely controlled by the insertion/deletion ( I/D ) polymorphism of the enzyme gene. The association among restenosis within coronary stents, plasma ACE level, and the I/D polymorphism is analyzed in the present prospective study. Methods and Results —One hundred seventy-six consecutive patients with successful, high-pressure, elective stenting of de novo lesions in the native coronary vessels were considered. At follow-up angiography, recurrence was observed in 35 patients (19.9%). Baseline clinical and demographic variables, plasma glucose and serum fibrinogen levels, lipid profile, descriptive and quantitative angiographic data, and procedural variables were not significantly different in patients with and without restenosis; mean plasma ACE levels (±SEM) were 40.8±3.5 and 20.7±1.0 U/L, respectively ( P &lt;.0001). Diameter stenosis percentage and minimum luminal diameter at 6 months showed statistically significant correlation with plasma ACE level ( r =.352 and −.387, respectively P &lt;.001). Twenty-one of 62 patients (33.9%) with D/D genotype, 13 of 80 (16.3%) with I/D genotype, and 1 of 34 (2.9%) with I/I genotype showed recurrence; the restenosis rate for each genotype is consistent with a codominant expression of the allele D . Conclusions —In a selected cohort of patients, both the D/D genotype of the ACE gene, and high plasma activity of the enzyme are significantly associated with in-stent restenosis. Continued study with clinically different subsets of patients and various stent designs is warranted.
Provision of age appropriate health services for young people has been ignored
Authors: R. Viner
Journal: BMJ (2000)

Plan represents considerable privatisationEditor-Dixon and Dewar's editorial welcomes the considerable injection of money promised in the NHS plan and claims that the plan is true to the NHS's founding principles. 1 Yet Aneurin Bevan's greatest achievement, and not one demanded of him by the Beveridge report, was the nationalisation of hospitals.He recognised that ownership was important, because with ownership comes control.The NHS plan promises 100 new hospitals by 2010 (69 of which are already in the pipeline).This will involve £7bn of new investment under the private finance initiative.Together with the new plans for some NHS operating to be carried out in the private sector, the NHS plan represents a larger privatisation than even the Tories planned.Curiously, the plan also recognises the failure of past privatisations.I remember unsuccessfully voting against the privatisation of cleaning at the London Hospital when I was a board member of the old Tower Hamlets Health Authority.Squalid wards followed, and they remain with us now.The plan recognises that this policy was a disaster.Altogether £30m of cash is to be injected into hospital trusts before the next election to pay for the consequences of this mistaken minor privatisation.How much money will we have to spend in five, 10, or 20 years' time to correct the disastrous policy of major privatisation that we are now heading for?Mr Milburn, think again, before it is too late.
The Human Immunodeficiency Virus and the Adrenal Medulla
Authors: CAROL D. WEISS
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 August 1986The Human Immunodeficiency Virus and the Adrenal MedullaCAROL D. WEISS, M.D.CAROL D. WEISS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-105-2-300_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Several reports over the past few years have called attention to the striking incidence of adrenal gland disease in patients with the acquired immunodeficiency syndrome (AIDS) (1-4). Adrenal inflammation, often with severe hemorrhagic necrosis, has been commonly observed at autopsy, frequently in association with coexistent cytomegalovirus infection of the gland. Similarly, adrenal insufficiency has been reported in patients with AIDS (5).In reviewing the autopsy reports of 32 patients with AIDS who died at St. Vincent's Hospital in the years 1981 to 1985, I found 15 cases with reported adrenal disease. All but 1 were associated with...References1. KLEINMANNFRIEDLANSURKS RDGM. Adrenocortical function in the acquired immunodeficiency syndrome [Letter]. Ann Intern Med. 1983;99:566. LinkGoogle Scholar2. MACHERREICHERTSTRAUSS ACS. Death in the AIDS patient: role of cytomegalovirus. N Engl J Med. 1983;309:1454. CrossrefMedlineGoogle Scholar3. TAPPERHEIDRUNLERNERAL' KHAFAJISEITZMAN MZCKP. Adrenal necrosis in the acquired immunodeficiency syndrome. Ann Intern Med. 1984;100:239-41. LinkGoogle Scholar4. GREENECOLEGREENE LWJ. Adrenal insufficiency as a complication of the acquired immunodeficiency syndrome. Ann Intern Med. 1984;101:497-8. LinkGoogle Scholar5. GUENTHNERRABINOWEVAN NIELNAFTILANDLUTHY ESAAR. Primary Addison's disease in a patient with the acquired immunodeficiency syndrome. Ann Intern Med. 1984;100:847-8. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: CAROL D. WEISS, M.D.Affiliations: St. Vincent's Hospital and Medical Center New York, NY 10011 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe HPA Axis and HIV InfectionInsuffisance surrénale périphérique au cours du sidaEndocrine Implications of Human Immunodeficiency Virus InfectionThe adrenal gland in AIDSHyponatremia in hospitalized patients with the acquired immunodeficiency syndrome (AIDS) and the AIDS-Related complexEndocrine Manifestations of Human Immunodeficiency Virus (HIV) InfectionMycobacterium avium-intracellulare and adrenal insufficiency in AIDSPathology of the pituitary gland in patients with the acquired immune deficiency syndrome (AIDS) 1 August 1986Volume 105, Issue 2Page: 300-300KeywordsAIDSAdrenal glandsAutopsyCytomegalovirus infectionHIVInflammationNecrosis ePublished: 1 December 2008 Issue Published: 1 August 1986 PDF downloadLoading ...
TINCTURE OF IODIN FOR THE UMBILICAL CORD
Authors: Joseph S. Lewis
Journal: JAMA (1910)

The increasing use of iodin suggested to me its application to the freshly severed umbilical cord. The tincture, as is well known, tends to form a dry iodin-impregnated scale or scab over any moist surface not giving off a purulent discharge, such as a clean varicose ulcer or a freshly sutured wound. The treatment to be described was tried on several infants with satisfactory results. In one case the cord was found mummified and separated on the fourth day, the granulated surface healed to a small dry scab within the same week. Others averaged ten days to two weeks for the entire process Iodism was not observed. The technic used is as follows: As soon as the cord is cut and tied, blood and vernix caseosa are wiped off with a sterile pledget. The stump is then painted with the official tincture until deeply stained; especially the cut end, the ligature,
Coronary Reserve of High- and Low-Flow Regions in the Dog Heart Left Ventricle
Authors: Robert Loncar, Christian W. Flesche, Andreas Deussen
Journal: Circulation (1998)

Background —Left ventricular myocardial blood flow is spatially heterogeneous. The hypothesis we tested was whether myocardial areas with a steady-state flow &lt;0.5 times mean flow are underperfused and areas with flow &gt;1.5 times mean flow are overperfused. Methods and Results —In anesthetized beagle dogs (n=10), the relationship between local blood flow versus S -adenosylhomocysteine (SAH) concentration, a measure of the free intracellular adenosine concentration, and lactate, a measure of the myocardial NADH/NAD + ratio, were determined under control conditions and after coronary constriction. Control local myocardial blood flow was 0.99±0.46 mL · min −1 · g −1 , with a coefficient of variation of 0.36±0.12 (n=256 per heart; sample wet mass, 125±30 mg). Tissue concentrations of SAH (3.4±2.5 nmol/g) and lactate (1.88±0.80 μmol/g) were not elevated in low-flow samples. However, after coronary artery constriction, poststenotic blood flow decreased from 1.00±0.27 to 0.49±0.22 mL · min −1 · g −1 ( P &lt;0.04), with significant correlation between local SAH and flow ( r =−0.59) and lactate and flow ( r =−0.50). Although nearly all samples from control high-flow regions showed increased SAH concentrations if relative flow after stenosis was &lt;1.0, control low-flow samples frequently displayed low SAH concentrations. The percent reduction in flow determined the changes in the local SAH and lactate concentration, independent of the local control blood flow. Conclusions —When the coronary inflow is unrestricted, the oxygen supply to control low-flow regions meets metabolic demand. Flow to control high-flow regions reflects a higher local demand rather than overperfusion. Thus, blood flow heterogeneity most likely reflects differences in aerobic metabolism.
THE GASTROINTESTINAL EXAMINATION
Authors: Gregory Connell
Journal: JAMA (1941)

<h3>To the Editor:—</h3> Dr. Ramsay Spillman's communication published inThe JournalApril 19 directs attention to certain fundamental difficulties such as the tendency to consider the roentgenologist as a technician rather than as a consultant. The matter of medical costs is, of course, another fundamental question. It would seem that the cost of poor results following improper and insufficient treatment based on incorrect or incomplete diagnosis may be found to exceed the cost of better results following proper and sufficient treatment based on more correct and complete diagnosis. "A proper examination of the complete tract" and of the entire patient will improve results and, by so doing, reduce costs.