tbuckley/cabot-search huggingface dataset:
Predicting Diabetes: Our Relentless Quest for Genomic Nuggets
Authors: Samuel Dagogo-Jack
Journal: Diabetes Care (2012)

The latest estimates from the Center for Disease Control and Prevention indicate that in 2010 approximately 26 million American adults had diabetes and 79 million had prediabetes (1). African Americans and other ethnic groups continue to suffer higher rates of diabetes than whites. Worldwide, diabetes affects 285 million adults (2). Type 2 diabetes accounts for ∼95% of all cases. The exact reasons for the diabetes epidemic, and its predilection for certain ethnic groups, are unknown. However, interactions between genetic predisposition and environmental triggers (or accelerants) are generally presumed to underlie the etiology of diabetes (3–5) (Fig. 1). The best known environmental risk factors are dietary habits, physical inactivity, and obesity; interventions that ameliorate these risk factors prevent the development of type 2 diabetes (6,7).



Figure 1 
Schematic of the pathogenesis of diabetes. Genetic and environmental factors, acting via complex immunological mechanisms, result in β-cell destruction that leads to type 1 diabetes. Gene-environment interactions also underlie susceptibility to type 2 diabetes, the pathophysiological hallmarks of which include insulin resistance and β-cell dysfunction.



By contrast, knowledge of the genetic basis of diabetes is incomplete, despite Herculean efforts (8–12). Genome-wide association studies have accelerated the discovery of single-nucleotide polymorphisms (SNPs) at numerous loci. Comparison of the frequencies of these SNPs in case-control studies has enabled the calculation of the odds of their association with specific disease phenotypes. To date, genome-wide studies have added more than 4,000 SNPs involving some 200 diseases, including >30 diabetes-related SNPs (diabetoSNPs). The analysis of diabetoSNPs has intrinsic appeal as a tool for diabetes prediction, and could also yield potential clues to ethnic disparities in the susceptibility to type 2 diabetes. Because the diabetoSNPs individually confer modest effects, investigators have adopted …
5-Hydroxytryptamine induces phospholipase C-mediated hydrolysis of phosphoinositides through 5-hydroxytryptamine-2 receptors in cultured fetal mouse ventricular myocytes.
Authors: Y Hamamori, M Yokoyama, M Yamada, H Akita, K Goshima, H Fukuzaki
Journal: Circulation Research (1990)

5-Hydroxytryptamine (5-HT) stimulates the rate and force of cardiac contraction. However, the molecular mechanisms of 5-HT actions on the heart are unknown. We examined effects of 5-HT on phospholipase C-mediated hydrolysis of phosphoinositides and its regulation in cultured fetal mouse ventricular myocytes labeled with [3H]inositol. Accumulation of inositol monophosphate, inositol bisphosphate, and inositol trisphosphate was assessed after stimulation with 5-HT, catecholamines, and AlF4-. Inositol bisphosphate and trisphosphate reached a peak at 15 minutes by 5-HT stimulation and at 30 minutes by AlF4- stimulation. Inositol monophosphate accumulated linearly for at least 30 minutes in the presence of LiCl. The 5-HT effect was dose dependent, and the threshold concentration was 0.1 microM with the half-maximum effective concentration of 1 microM. Ketanserin in nanomolar concentrations inhibited the phospholipase C reaction by 100 microM 5-HT with the half-maximum inhibitory concentration of 0.5 nM. Pertussis toxin (100-1,000 ng/ml) did not influence the phospholipase C reaction by 5-HT, but it partially inhibited the reaction by AlF4-. Protein kinase C-activating phorbol esters like 12-O-tetradecanoylphorbol 13-acetate (TPA) and phorbol 12,13-dibutyrate, but not 4 alpha-phorbol 12,13-didecanoate, which is inactive for protein kinase C, completely inhibited the reaction by 5-HT; TPA showed 30% inhibition on the reaction by AlF4-. The magnitude of accumulated inositol phosphates by AlF4- was at least several times greater than that by 5-HT. Norepinephrine- and epinephrine-stimulated phospholipase C reactions were completely abolished by prazosin. These results suggest that 5-HT directly stimulates phospholipase C-mediated hydrolysis of phosphoinositides through 5-hydroxytryptamine-2 (5-HT2) receptors in the ventricular myocytes and that this reaction is negatively regulated by protein kinase C. 5-HT2 receptors may be coupled to phospholipase C via a pertussis toxin-insensitive GTP-binding protein in the myocytes.
Carotid Intima-Media Thickness and Plasma Asymmetric Dimethylarginine in Mexican Children Exposed to Inorganic Arsenic
Authors: Citlalli Osorio-Yáñez, Julio C. Ayllon-Vergara, Guadalupe Aguilar-Madrid, Laura Arreola-Mendoza, Erika Hernández-Castellanos, Angel Barrera-Hernández, Andrea De Vizcaya-Ruiz, Luz M. Del Razo
Journal: Environmental Health Perspectives (2013)

Arsenic exposure is a risk factor for atherosclerosis in adults, but there is little information on arsenic and early risk biomarkers for atherosclerosis in children. Carotid intima-media thickness (cIMT) is an indicator of subclinical atherosclerotic burden that has been associated with plasma asymmetric dimethylarginine (ADMA), a predictor of cardiovascular disease risk.The aim of this study was to investigate associations of arsenic exposure with cIMT, ADMA, and endothelial adhesion molecules [soluble intercellular cell adhesion molecule-1 (sICAM-1); soluble vascular cell adhesion molecule-1 (sVCAM-1)] in children who had been exposed to environmental inorganic arsenic (iAs).We conducted a cross-sectional study in 199 children 3-14 years of age who were residents of Zimapan, México. We evaluated cIMT using ultrasonography, and plasma lipid profiles by standard methods. We analyzed ADMA, sICAM-1, and sVCAM-1 by ELISA, and measured the concentrations of total speciated arsenic (tAs) in urine using hydride generation cryotrapping atomic absorption spectrometry.In the multiple linear regression model for cIMT, tAs categories were positively associated with cIMT increase. The estimated cIMT diameter was greater in 35- to 70-ng/mL and > 70-ng/mL groups (0.035 mm and 0.058 mm per 1-ng/mL increase in urinary tAs, respectively), compared with the < 35-ng/mL group. In addition to tAs level, plasma ADMA was a significant predictor of cIMT. In the adjusted regression model, cIMT, percent iAs, and plasma sVCAM-1 were significant predictors of ADMA levels (e.g., 0.419-μmol/L increase in ADMA per 1-mm increase in cIMT).Arsenic exposure and plasma ADMA levels were positively associated with cIMT in a population of Mexican children with environmental arsenic exposure through drinking water.
The Infant Health and Development Program: Results at 8 Years
Authors: Martin C. Carr
Journal: JAMA (1997)

To the Editor.  —McCarton et al 1 present impressive data clearly showing that a 3-year early intervention program failed to produce any significant or meaningful improvement in cognitive function or academic achievement when each child was evaluated at age 8 years. Even at age 5 years, there was little if any improvement, and the present follow-up found even less than before. One is tempted to predict that a follow-up at age 12 years would find imperceptible differences among the groups.  These findings bring into question the conclusion by McCarton et al that this study indicates a need to develop additional intervention strategies for LBW children that can provide sustained benefits. This well-designed, well-executed, and expensive trial seriously challenges the validity of the strategies used here, since it failed to provide any long-term improvement. The outcome of this investigation suggests that merely revising the disproved strategies used here would be wasting time and money.
Effects of Ca++ and Prostaglandin E1 on Vasopressin Activation of Renal Adenyl Cyclase
Authors: Fumiaki Marumo, Isidore S. Edelman
Journal: Journal of Clinical Investigation (1971)

Adenyl cyclase activity was assayed in crude homogenates of the renal cortex, medulla, and papilla of the golden hamster. The specific activity (moles C-AMP/unit of time per mg protein of tissue) of the enzyme under basal conditions, was greatest in papilla, somewhat lower in medulla, and least in cortex. On an absolute scale, the sensitivity to vasopressin was greater in the medullary and papillary than in the cortical homogenates. In addition, at concentrations of 0.1-1.0 mm, CaCl(2) inhibited the enzyme in the order papilla > medulla > cortex. These results imply the existence of distinct differences in the composition of the adenyl cyclase-receptor complex in various parts of the kidney. We proposed that Ca(++) inhibits the core enzyme directly since at the minimally inhibitory concentration (0.1 mm), CaCl(2) reduced to an equivalent extent (a) basal activity, (b) the response to graded doses of vasopressin (0.5 to 50.0 mU/ml) and (c) the response to maximal stimulatory concentrations of NaF (10 mm). Prostaglandin E(1) (PGE(1) = 10(-7)m) had no effect on either basal adenyl-cyclase activity or the response to 10 mm NaF in medullary and papillary homogenates. 7-Oxa-13-prostynoic acid (10(-4)m) similarly had no effect under basal conditions or on stimulation with NaF in medullary homogenates. Both fatty acids, however, inhibited the enzymic response to vasopressin, particularly at low concentrations of the peptide. The straight-chain fatty acid, 11-eicosanoic acid (10(-7)m), was inactive on basal activity or on the response to vasopressin. The possibility that PGE(1) modifies the coupling mechanism between the core enzyme and the hormone-specific receptor is discussed.
Information systems for general practitioners for quality assessment: II. Information preferences of the doctors.
Authors: R C Fraser, J T Gosling
Journal: BMJ (1985)

In this part of the study we intended to determine (a) the extent to which currently supplied information was used by general practitioners to assess their performance and (b) the preferences of the doctors for new information. Four aspects of professional activity were investigated: prescribing, practice activity as shown by family practitioner committee quarterly returns, hospital use, and audit in depth. The results are from 508(76%) questionnaires returned from the 669 general practitioners circulated in Leicestershire and Lincolnshire. The prescribing habits of most doctors are influenced both by factual information about drugs from many sources and by feedback on their personal prescribing or that of their practice, which is supplied by the Prescription Pricing Authority, particularly regarding prescribing costs. Little use is made of data from the family practitioner committee. A distinct pattern of preferences for particular items of information emerged. Most doctors wished to receive information that would enable them to compare their personal performance or that of their practice with their local colleagues from the Prescription Pricing Authority (66%), the family practitioner committee (58%), and hospital sources (57%). Because doctors chose particular items of information that they would like to have, systems that are developed to provide such information are likely to be used. The need to incorporate comparison with peers is particularly important.
Henry Gemmell Morgan
Authors: Jim Shepherd, Alan Shenkin
Journal: BMJ (2007)

Geoffrey Barker first worked in a neurological team dealing with head injuries from the D-Day landings.In 1948 he joined Tooting Bec Hospital, introducing an opendoor policy in the day hospital and setting up the art therapy department.He specialised in women's mental health and drug abuse, and during 1967-72 was medical administrator.Geoffrey was a tutor at the Tavistock Clinic and held a child guidance fellowship at Guy's Hospital.He was adviser to the Arts Council, chairman of the Dyslexia Teaching Centre, and a founding member of the Alzheimer's Society.On his retirement he continued to work with the Alzheimer's Society, running a carers group from his home for many years, and for MIND, Crossroads, and Carers UK.A Barker
Controlling Rubella: Problems and Perspectives
Authors: DOROTHY M. HORSTMANN
Journal: Annals of Internal Medicine (1975)

Long-term effectiveness of rubella vaccination in childhood is of particular importance because the ultimate goal of immunization is the prevention of infection during pregnancy. To determine how well vaccine-induced immunity persists in comparison to that acquired naturally, several hundred susceptible children who seroconverted after receiving HPV77DE5 vaccine were followed serologically over a 3-to-5-year period. The results indicate that vaccine-induced antibodies are less stable than those acquired through natural infection, and their persistence is closely related to the original response to immunization. Thus children who responded with a broad range of antibody types and who had brisk postvaccinal hemagglutination-inhibiting antibody titers of greater than or equal to 1:64, maintained such levels without significant decline. In contrast, among the children who had feeble hemagglutination-inhibiting antibody responses initially and failed to develop complement-fixing or precipitating antibodies, a significant proportion lost detectable hemagglutination-inhibiting antibody levels after 3 to 5 years. The current and future immunity of such children is therefore in doubt, unless natural reinfection with wild rubella virus or revaccination with a more effective vaccine corrects their antibody deficiencies.
Shigella sonnei Bacteremia
Authors: B. V. Winter
Journal: JAMA (1962)

A 25-year-old septic-system excavator was hospitalized for treatment of severe dysentery. Cultures from blood and feces were positive for<i>Shigella sonnei</i>, an organism not previously reported as invading the blood stream of an adult. The occurrence of specific infection was retrospectively documented by special immunological studies. Increased awareness of bacteremia as a possible complication of Shigella infections will perhaps prompt more frequent culture of the blood from patients with dysentery in the future. If so, the recent apparent increase in bacterial enteric infections will provide an opportunity to establish the actual incidence and importance of blood stream invasion by the Shigella. The patient in this case was free from diarrhea on the 11th day of hospitalization and was released on the 14th day, after 3 successive fecal cultures had been reported negative.
Lung abscess in a professional rugby player: an illustration of overtraining syndrome?
Authors: Bernard H Castinel, Philippe Adam, Christophe Prat, Pierre Mourlanette
Journal: British Journal of Sports Medicine (2007)

As in other endurance sports, the intensity of training sessions and the pace of competition has significantly increased since rugby union became a professional sport. The case history is presented of a professional rugby player who was diagnosed with septicaemia and a lung abscess following an infected wound to the ear. The symptoms only resolved after a large dose of antibiotics and 3 months of rest. It is hypothesised that this may be an example of overtraining syndrome, but complementary blood analyses would be necessary to confirm this. The case underlines the importance of clinically assessing the individual capacity of players to recover, in order to prevent overtraining and to maintain a high level of performance during the whole season.
ACTION OF ALCOHOL.
Authors: P. H. Cronin
Journal: JAMA (1884)

<h3>To the Editor:—</h3> In the last issue of your valuable journal, a somewhat brief synopsis of a clinical lecture delivered by me, served as the basis of an editorial notice, that, though accepted by me with all the meekness that should characterize the bearing of a junior hearkening to the voice of a "father in Israel," bears within it a few elements of error. In speaking of the combustible power of alcohol, as compared with that of cod-liver oil, I instanced an experiment not unfamiliar to chemists of to-day, and which was no doubt familiar to Baron Liebig. Indeed, we know that alcohol must be rich in heatproducing power, its chemical formula (C<sub>2</sub>H<sub>6</sub>O), ethyl hydrate, clearly justifying such an opinion. Its power in raising the temperature of water was referred to by me, and an application of the knowledge of this fact served in part
Effects of ambulance transport in critically ill patients.
Authors: G Waddell, P D Scott, N W Lees, I M Ledingham
Journal: BMJ (1975)

Two groups of critically ill patients were transferred by ambulance from other hospitals to a central intensive therapy unit. The effect of transport was reviewed retrospectively in 46 patients and prospectively in 20 patients. Of the 46 patients reviewed retrospectively six became hypotensive, six became hypertensive, and seven developed delayed hypotension. One patient developed fits and six out of 13 patients had a rise in arterial PCO-2 of 1-6-4-1 kPa (12-31 mm Hg). Of the 20 patients reviewed prospectively, one patient became hypertensive due to overtransfusion, one had a fit, but none became hypotensive. Three out of four cases of delayed hypotension were related to starting intermittent positive pressure ventilation. Arterial PCO-2 fell in one patient and arterial PCO-2 rose in two, each change being related to changed oxygen therapy or narcotics. There were no changes in other cardiovascular or respiratory indices, body temperature, or urine production. Earlier transfer, resuscitation before transfer, continuing medical care during the journey, and hence a slower smoother journey seemed to be important factors in the management of these patients. Our findings, may have important implications in the future regional organization of the care of critically ill patients.
Rifamycin SV and rifampicin exhibit differential inhibition of the hepatic rat organic anion transporting polypeptides, Oatp1 and Oatp2
Authors: Karin Fattinger, Valentino Cattori, Bruno Hagenbuch, Peter J. Meier, Bruno Stieger
Journal: Hepatology (2000)

The antibiotics, rifamycin SV and rifampicin, are known to interfere with hepatic bile salt and organic anion uptake. The aim of this study was to explore which transport systems are affected. In short-term-cultured rat hepatocytes, low concentrations (10 micromol/L) of both compounds inhibited mainly sodium-independent taurocholate uptake, whereas higher concentrations (100 micromol/L) also inhibited sodium-dependent taurocholate uptake. In Xenopus laevis oocytes expressing the Na(+)/taurocholate cotransporting polypeptide (Ntcp), high rifamycin SV and rifampicin concentrations were required for inhibition of taurocholate uptake. In contrast, sodium-independent taurocholate uptake mediated by the organic anion transporting polypeptides, Oatp1 and Oatp2, was already substantially inhibited by 10 micromol/L rifamycin SV. Rifampicin potently inhibited Oatp2-mediated taurocholate uptake, but did not interfere with Oatp1-mediated taurocholate uptake. Similar effects of rifamycin SV and rifampicin were found for Oatp1- and Oatp2-mediated estradiol-17beta-glucuronide transport. Dixon plot analysis yielded a pattern compatible with competitive inhibition of estradiol-17beta-glucuronide transport with K(i) estimates of 6.6 micromol/L and 7.3 micromol/L for rifamycin SV-induced inhibition of Oatp1 and Oatp2, respectively, and of 1.4 micromol/L for rifampicin-induced inhibition of Oatp2. These results demonstrate that rifamycin SV and rifampicin exhibit differential inhibition on Oatp1 and Oatp2, and identify rifampicin as a selective Oatp2 inhibitor. The data indicate that these inhibitors can be used to determine the in vivo relevance of Oatp1 and Oatp2 for the overall bioavailability and disposition of drugs and other Oatp1/2 substrates.
Health Care in America: An Intimate Glimpse
Authors: Byron Farwell
Journal: Annals of Internal Medicine (1996)

On Being a Patient15 December 1996Health Care in America: An Intimate GlimpseByron FarwellByron FarwellHillsboro, VA 20134.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-12-199612150-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail I am an obese 75-year-old man. I recently had a large cyst removed from my spine, along with some bits of bone for which the surgeon said I had no need. The surgeon, trained at the University of Pennsylvania and Harvard, had an impressive resume and came highly recommended. He was, in addition, a very likable fellow. He looked about 18 years old.I had last had surgery 30 years earlier in Switzerland, where I had a large room with a window overlooking the Alps in a hospital that boasted a splendid wine cellar. The nurses, efficient and caring, even ... Author, Article, and Disclosure InformationAuthors: Byron FarwellAffiliations: Hillsboro, VA 20134.Corresponding Author: Byron Farwell, Box 3200 C, Hillsboro, VA 20134. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byA Call to Looms 15 December 1996Volume 125, Issue 12Page: 1005-1006KeywordsAllopurinolBloodCathetersFoodHealth careNursesPenisSaltsSurgeonsSurgery ePublished: 15 August 2000 Issue Published: 15 December 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Role of serum free light chains in predicting HIV‐associated non‐Hodgkin lymphoma and Hodgkin's lymphoma and its correlation with antiretroviral therapy
Authors: Michele Bibas, Maria Paola Trotta, Alessandro Cozzi‐Lepri, Patrizia Lorenzini, Carmela Pinnetti, Giuliano Rizzardini, Gioacchino Angarano, Pietro Caramello, Laura Sighinolfi, Claudio Maria Mastroianni, Giovanni Mazzarello, Antonino Di Caro, Cristina Di Giacomo, Antonella d'Arminio Monforte, Andrea Antinori
Journal: American Journal of Hematology (2012)

A nested case-control study was performed within the Italian cohort of naïve to antiretroviral human immunodeficiency virus (HIV) patients (ICONA) cohort to evaluate the role of serum free light chains (sFLC) in predicting non-Hodgkin's lymphoma (NHL) and Hodgkin lymphoma (HL) in HIV-infected individuals. Of 6513 participants, 86 patients developed lymphoma and 46 of these (NHL, 30; HL, 16) were included in this analysis having stored prediagnostic blood. A total of 46 serum case samples matched 1:1 to lymphoma-free serum control samples were assayed for κ and λ sFLC levels and compared by using conditional logistic regression. Because the polyclonal nature of free light chains (FLCs) was the focus of our study, we introduced the k + λ sum as the measurement of choice and as the primary variable studied. κ + λ sFLC values were significantly higher in patient with lymphoma than in controls, especially when considering samples stored 0-2-year period before the lymphoma diagnosis. In the multivariable analysis, the elevation of sFLC predicted the risk of lymphoma independently of CD4 count, (odd ratio of 16.85 for k + λ sFLC >2-fold upper normal limit (UNL) vs. normal value). A significant reduction in the risk of lymphoma (odd ratio of 0.07 in model with k + λ sFLC) was found in people with low sFLC and undetectable HIV viremia lasting more than 6 months. Our analysis indicates that an elevated polyclonal sFLC is a strong and sensitive predictor of the risk of developing lymphomas, and it is an easy to measure biomarker that merits consideration for introduction in routine clinical practice in people with HIV.