tbuckley/cabot-search huggingface dataset:
Regulation of vascular endothelial growth factor expression by insulin-like growth factor-II in human keratinocytes, differential involvement of mitogen-activated protein kinases and feedback inhibition of protein kinase C
Authors: H.J. Kim, T-Y. Kim
Journal: British Journal of Dermatology (2005)

Background Vascular endothelial growth factor (VEGF) is overexpressed in hyperproliferative diseases such as psoriasis and cancer, which are characterized by an increased angiogenesis. It was reported that insulin‐like growth factor (IGF)‐II is highly expressed during hepatocarcinogenesis and is increased in psoriatic lesions. The increase in IGF‐II is believed to be associated with the pathogenesis of these diseases by increasing angiogenesis. Objectives In order to investigate the relationship between IGF‐II and angiogenesis‐related VEGF, VEGF expression in the IGF‐II‐treated human keratinocytes was monitored and the IGF‐II signalling pathways were examined with respect to VEGF expression. Methods Northern blot analysis for the VEGF mRNA levels and an enzyme‐linked immunosorbent assay for the VEGF protein were performed to determine if IGF‐II (100 ng mL−1) can increase the VEGF expression levels with or without a pretreatment with protein inhibitors in primary normal human keratinocytes and HaCaT cells. Results The mRNA and protein levels of VEGF by IGF‐II were increased in a time‐dependent manner and reached the maximum level 2 h and 8 h after the IGF‐II treatment, respectively. However, this increase was abrogated by pretreatment with an extracellular signal‐regulated kinase (ERK) inhibitor but not by a p38 inhibitor. The IGF‐II‐mediated VEGF induction was also effectively inhibited by a pretreatment with the tyrosine kinase inhibitor and Src inhibitor. The PI3–kinase inhibitor also inhibited the expression of VEGF by IGF‐II. However, the phospholipase C (PLC) and protein kinase C (PKC) inhibitors did not block the increases of VEGF mRNA level and its protein level by IGF‐II, and the PKC inhibitor instead increased VEGF expression by IGF‐II. Conclusions These results suggest that the tyrosine kinase–Src–ERK1/2 pathway and the PI3–kinase pathway are involved in IGF‐II‐mediated VEGF expression, but PKC is negatively associated in the IGF‐II‐mediated VEGF expression.
The British standard series of contact dermatitis allergens: validation in clinical practice and value for clinical governance
Authors: J.E.R. Britton, S.M. Wilkinson, J.S.C. English, D.J. Gawkrodger, A.D. Ormerod, J.E. Sansom, S. Shaw, B. Statham
Journal: British Journal of Dermatology (2003)

Summary Background All centres use an empirically determined set of ‘standard’ test allergens for patch testing that contain the commoner environmental sensitizers. Objectives To assess the validity of the British standard series of 12 allergens used in addition to the 23 already in the European standard series. Patients and Methods Results for 3062 consecutive patients patch tested in seven centres across the United Kingdom during the year 2000 were analysed. Results The additional allergens from the British series and positive rates were: methyl dibromoglutaronitrile 2·4%, carba mix 1·6%, tixocortol pivalate 1·5%, ethylenediamine 1·3%, cetearyl alcohol 0·8%, 2‐bromo‐2‐nitropane‐1,3‐diol 0·8%, diazolidinyl urea 0·7%, chlorocresol 0·6%, budesonide 0·6%, fusidic acid 0·5%, imidazolidinyl urea 0·5%, and chloroxylenol 0·4%. The allergens with the lowest positive rate in the European standard series were primin at 0·6% and isopropyl‐phenyl‐para‐phenylenediamine at 0·4%. Conclusions The 12 allergens in the British series should continue being tested as a standard addition to the European series within the U.K. The collection of data in this manner to allow comparisons between centres shows differences that reflect selection criteria and interpretation of results, and offers a useful tool for audit and clinical governance. Testing fewer than 1 : 2150 population may indicate underprovision of service. Similarly, rates of sensitization for nickel contact allergy above 26% and for fragrance mix above 16% (the upper 95% confidence intervals) should stimulate inquiry into the reasons behind this.
Role of proto-oncogene activation in carcinogenesis.
Authors: M W Anderson, S H Reynolds, M You, R M Maronpot
Journal: Environmental Health Perspectives (1992)

The accumulation of genetic damage in the forms of activated proto-oncogenes and inactivated tumor-suppressor genes is the driving force in the evolution of a normal cell to a malignant cell. For example, both the activation of ras oncogenes and the inactivation of several suppressor genes, including p53, have been observed in the development of human colon and lung tumors. Point mutations in key codons can activate ras proto-oncogenes and inactivate the p53 suppressor gene. Thus, several critical genes for tumorigenesis are potential targets for carcinogens and radiation that can induce point mutations at low doses. The ras proto-oncogenes are targets for many genotoxic carcinogens. Activation of the ras gene is an early event--probably the
THE ANTIBODY RESPONSE OF RABBITS TO INJECTIONS OF EMULSIONS AND EXTRACTS OF HOMOLOGOUS BRAIN
Authors: Francis F. Schwentker, Thomas M. Rivers
Journal: The Journal of Experimental Medicine (1934)

Rabbits injected with fresh emulsions of homologous brain developed few or no antibodies capable of fixing complement in the presence of aqueous emulsions or alcoholic extracts of rabbit brain. Complement-fixing antibodies, however, were produced in rabbits by means of injections (1) of sterile emulsions of homologous brain which had been allowed to stand at room temperature for 5 to 30 days and (2) of emulsions of homologous brain experimentally infected with vaccine virus. The antisera that were produced following injections of emulsions of autolyzed homologous brain were shown by absorption tests to contain both specific and non-specific antibodies. The specific brain antigen was found to be approximately six times as abundant in the white matter as in the grey. It was almost absent from the brain of fetal and newly born rabbits, but increased in amount with the age of the animal to reach a maximum concentration at maturity. The specific antigen seemed to parallel the myelin content of brain tissue.
Act II — Curve Bending
Authors: Daniel Y. Patterson
Journal: New England Journal of Medicine (2009)

Health care reform seems to be a two-act play. We are moving toward the conclusion of the first act, universal coverage. The second act will consist of controlling the cost of health care, or “bending the cost curve.”A recent article by Atul Gawande traced the historical development of universal coverage in England, France, and Switzerland.1 These countries' solutions were all “path-dependent,” which suggests that the final outcome of universal coverage in the United States and the manner in which care will be delivered here will evolve from the path or paths that have been grooved by our country's historical . . .
Coronary Heart Disease and Prevention in the United States
Authors: Jeremiah R. Brown, Gerald T. O'Connor
Journal: New England Journal of Medicine (2010)

Heart disease remains the leading cause of death in the United States: in 2006, it resulted in 631,636 deaths in this country.1 Coronary heart disease accounts for 68% of these deaths and affects more than a million Americans each year.2 Common risk factors for coronary heart disease include hypertension, high cholesterol levels, cigarette smoking, obesity, and a family history of heart disease. Most of these risk factors are modifiable by means of a healthy lifestyle or medication,2 and indeed, the rate of death due to heart disease has been decreasing since 1950 thanks to reductions in cigarette smoking and hypertension. . . .
Changes in Total Body Calcium and Sodium in Osteomalacia
Authors: D. J. Hosking, M. J. Chamberlain, J. H. Fremlin, H. James
Journal: BMJ (1972)

Serial measurements were made of total body calcium and sodium, using whole body neutron activation analysis, in six patients being treated for osteomalacia. All showed a rise in total body calcium ranging from 3 to 30%; this continued for up to 24 months after the start of treatment, though complete healing had apparently occurred after 6 months on the basis of histological examination of biopsy specimens of bone. As the total body calcium rose there was a fall in the non-exchangeable sodium pool in bone.
Chronic Intrahepatic Cholestasis With Granulomas and Biliary Cirrhosis
Authors: Eapen Thomas
Journal: JAMA (1977)

CHRONIC intrahepatic cholestasis, a syndrome characterized by jaundice, pruritus, and hepatomegaly, may occur as a result of a variety of causes. When associated with hepatic granulomas, many cases are due to adverse drug reactions, Hodgkin's disease, Crohn's disease, and postnecrotic cirrhosis, and these are relatively easily distinguished. Infections from viral agents, brucellosis and Q fever, and fungi may be excluded as causes by appropriate tests. Tuberculosis may be difficult to prove at times. Primary biliary cirrhosis, which also is seen generally as chronic intrahepatic cholestasis, may be closely mimicked by the cholestasis that has been recently noted to rarely occur in patients with sarcoidosis.<sup>1,2</sup>Advanced states of the two diseases may be indistinguishable, as exemplified by the patient described here. <h3>Report of a Case</h3> A 62-year-old woman was admitted to Westchester County Medical Center on April 23, 1976, for investigation of pruritus and elevated serum alkaline phosphatase values. The patient,
Management of bedwetting in children and young people: summary of NICE guidance
Authors: V. D. Nunes, N. O'Flynn, J. Evans, L. Sawyer
Journal: BMJ (2010)

Bedwetting is a widespread and distressing condition that can have a deep impact on a child or young person’s behaviour, emotional wellbeing, and social life.1 2 It is also very stressful for the parents or carers, generating a sense of helplessness, lack of hope and optimism,2 feelings of being different from others, feelings of guilt and shame, humiliation, victimisation, and loss of self esteem.3 4 The prevalence of bedwetting decreases with age. The Avon longitudinal study found that bedwetting on more than two nights a week occurs in 8% of children aged about 4 years 6 months and in 1.5% of those aged 9 years 6 months.5 This article summarises the recommendations from the most recent guidance from the National Institute for Health and Clinical Excellence (NICE) on the management of bedwetting in children and young people aged up to 19 years.6 NICE recommendations are based on systematic reviews of best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Information for children and families
Glycoforms of human endothelial CD34 that bind L-selectin carry sulfated sialyl Lewis x capped O- and N-glycans
Authors: Gerard Hernandez Mir, Jari Helin, Kari-Pekka Skarp, Richard D. Cummings, Antti Mäkitie, Risto Renkonen, Anne Leppänen
Journal: Blood (2009)
Quantitative evaluation of telomerase activity in small liver tumors: analysis of ultrasonography-guided liver biopsy specimens
Authors: Hiroshige Kojima, Osamu Yokosuka, Naoya Kato, Shuichirou Shiina, Fumio Imazeki, Hiromitsu Saisho, Yasushi Shiratori, Masao Omata
Journal: Journal of Hepatology (1999)
Effects of dexamethasone on albumin and collagen gene expression in primary cultures of adult rat hepatocytes
Authors: Douglas M. Jefferson, Lola M. Reid, Marie-Adele Giambrone, David A. Shafritz, Mark A. Zern
Journal: Hepatology (1985)

To further our studies on collagen gene expression, we have evaluated the molecular basis for the finding that steroids decrease collagen synthesis in cultured hepatocytes. We studied the effects of dexamethasone on primary cultures of adult rat hepatocytes grown on tissue culture plastic in either serum-supplemented medium or a serum-free hormonally defined medium. Cells were plated and allowed to attach for 24 hr in a mixture of serum-supplemented medium + hormonally defined medium. Cultures were then fed every 24 hr for 4 days under 1 of 4 conditions: serum-supplemented medium, serum-supplemented medium + dexamethasone, hormonally defined medium or hormonally defined medium + dexamethasone. On the fifth day, RNA was extracted. Dexamethasone did not affect the amount of RNA isolated; nor did it influence the quantitative translation of the mRNA in the rabbit reticulocyte lysate mRNA-dependent system. Employing hybridization analysis, dexamethasone resulted in increased albumin mRNA content in hepatocytes grown in serum-supplemented medium but had no affect on hormonally defined medium, and decreased type I in collagen mRNA content in cells grown in either serum-supplemented medium or hormonally defined medium. In cells cultured in hormonally defined medium, the β-actin and procollagen mRNA levels were lower than those in serum-supplemented medium, but albumin mRNA levels were higher, and in fact equivalent to those in vivo. β-Actin mRNA levels were not affected by dexamethasone in either serum-supplemented medium or hormonally defined medium. These results suggest that hormonally defined medium improves the expression of tissue-specific functions in hepatocytes, and dexamethasone reduces Type I collagen mRNA content in hepatocytes as well as mesenchymal cells. It is presently not clear whether the changes in albumin and collagen steady state mRNA levels are due to transcriptional and/or post-transcriptional controls.
Association Between Glycemia, Serum Lipoproteins, and the Risk of Oral Leukoplakia
Authors: Peter Meisel, Michael Dau, Wolfgang Sümnig, Birte Holtfreter, Mohammad Houshmand, Matthias Nauck, Thomas Kocher
Journal: Diabetes Care (2010)

OBJECTIVE Oral leukoplakia is an oral lesion with a premalignant character. Besides smoking and alcohol, diabetes could be a risk factor. The aim is to search for such an association. RESEARCH DESIGN AND METHODS Subjects with leukoplakia (N = 123) from the population-based Study of Health in Pomerania (SHIP) were matched 1:2 for age and sex with unaffected control subjects. Behavioral and lifestyle factors were assessed by a questionnaire. Lipoprotein concentrations, glycemia, and inflammation parameters were determined. RESULTS Subjects with oral leukoplakia showed higher levels of diabetes-related metabolites, a higher LDL/HDL cholesterol ratio (P = 0.004), and higher A1C (P = 0.002), and they were more frequently smokers (P &amp;lt; 0.001). Assessed by conditional logistic regression, the probability of leukoplakia increases with current smoking (odds ratio 2.20 [95% CI 1.16–4.17]) and higher levels of A1C (1.51 [95% CI 1.08–2.12]), revealing interaction between both factors (P = 0.012). CONCLUSIONS Diabetes is associated with the risk of oral leukoplakia, which is exaggerated by smoking. The risk is positively correlated with A1C concentrations.
Population based intervention to change back pain beliefs: three year follow up population survey
Authors: Rachelle Buchbinder, Damien Jolley
Journal: BMJ (2004)

We previously reported the positive results of a population based campaign designed to alter beliefs about back pain in Victoria, Australia. 1 2 The campaign consisted of television commercials which gave clear advice about back pain-for example, stay active and exercise, do not rest for prolonged periods, and stay at work.After the intervention, doctors' and the community's beliefs about back pain became significantly more positive, and the number of workers' claims for compensation and medical payments for back pain had declined.To measure sustained change in beliefs about back pain three years after the campaign ended, we repeated telephone surveys in Victoria and in adjacent New South Wales as a control.
Consumer Reports in Health Care
Authors: Daniel R. Longo
Journal: JAMA (1997)

Consumer reports in health care are a relatively recent phenomenon. Primarily designed to assist consumers in making more informed decisions about their personal health care, they appear to have an important by-product-they led to positive changes in the behavior of clinicians and health care delivery organizations. While there has been much speculation on their impact on health care consumer behavior, consumer reports offer an effective strategy in improving the quality of patient care.To examine the impact of an obstetrics consumer report developed and issued by the Missouri Department of Health on hospital behavior.A retrospective study of hospital behavior using both primary survey and secondary clinical data.Consumer reports were issued in 1993 to all Missouri hospitals providing obstetrical services (n=90). A survey was conducted a year later, and the results were analyzed with other available data to determine the effect of the report. Two hospitals discontinued obstetrical services by the time of the survey; of the remaining 88 hospitals, 82 (93%) responded to the survey.The following outcomes were examined: (1) number and percentage of hospitals that previously did not have services at the time report was issued, but had, or planned to have, services after a guide was published; (2) the percentage of obstetrical policies that were changed, planned to change, or are under discussion for change (car seat program, obstetrical follow-up services, formal transfer agreement, nurse educator for breast-feeding, and availability of tubal ligations); and (3) clinical outcomes, including satisfaction, appropriateness of charges, and the rates of cesarean delivery, high-risk infant transfer, ultrasound, vaginal birth after cesarean, very low birth weight, and newborn death.Within 1 year of the report, approximately 50% of hospitals that did not have car seat programs, formal transfer agreements, or nurse educators for breast-feeding prior to the report either instituted or planned to institute these services. Hospitals in competitive markets that did not offer one of these services at the time of the report were more likely to institute a service and/or were about twice as likely to consider improving several indicators. Clinical outcome indicators all improved in the expected direction.Public release of consumer reports may be useful not only in assisting consumers to make informed health care choices, but also in facilitating improvement in the quality of hospital services offered and care provided. Changes occur especially in competitive markets.
THE PURIFICATION AND CONCENTRATION OF DIPHTHERIA TOXOID
Authors: Augustus Wadsworth, James J. Quigley, Gretchen R. Sickles
Journal: The Journal of Experimental Medicine (1932)

By precipitation with acetone at 4 degrees C. a refined diphtheria toxoid was obtained as a dry powder, readily soluble in aqueous solutions. The powder itself appears to be stable. When dissolved in half the original volume of physiological salt solution, the toxoid remained stable, in the cold room, for a period of 7 months. Only toxoids should be used which have been completely detoxified by the treatment with formalin. The formalin is immediately and completely removed by precipitation with acetone. Filtration through a Mandler filter or the addition of a preservative did not appear to have any deleterious effect. Incubating at 39 degrees C. and freezing for 20 hours did not impair its activities. The flocculating value of the purified toxoid containing phenol was almost completely destroyed by freezing, while when merthiolate was the preservative, it was unchanged. Approximately 62 per cent of the nitrogen was eliminated in the process with approximately 15 per cent loss in flocculating value. The flocculating values were nearly double those of the original material and thus corresponded with the concentration, which was onehalf the volume. By this method, the antigenic activity of a toxoid below standard may be increased to a satisfactory standard. The antigenic activity of the refined product in the immunization of guinea pigs may in general parallel its flocculating values but the relation between the results of these tests may not be proportional nor constant. As an immunizing agent in the guinea pig, the refined toxoid possesses an antigenic activity that is equal to, or greater than, that of the unconcentrated toxoid.
An open letter to the General Medical Services Committee
Authors: M Townend
Journal: BMJ (1983)

any dose response relation which might be present in the remaining patients.The question needing an answer is whether patients with hypertension which is uncontrolled by acebutolol plus (say) hydrochlorothiazide 12 5 mg daily will benefit from an increase in dose to (say) 25 mg daily.To answer this all patients with blood pressure controlled by acebutolol alone and all those controlled by acebutolol plus hydro- chlorothiazide 12 5 mg daily must be excluded from study.Those uncontrolled by acebutolol plus hydrochlorothiazide 12 5 mg daily should be randomly allocated to continue on 12-5 mg daily or to increase to 25 mg daily, preferably in a parallel group design,' and certainly in sufficient numbers to ensure that a negative study really does mean no difference between the doses."Until we have results from valid studies of this type any statement about the ceiling antihypertensive dosage of thiazides or other antihypertensive drugs is unjustified and could be seriously misleading.
Radiographic and pathologic correlation of coal workers' pneumoconiosis.
Authors: V Vallyathan, P S Brower, F H Green, M D Attfield
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The relationships between chest radiographs (CXR) and corresponding pathology were investigated in 430 autopsied coal miners from West Virginia. Whole-lung sections were reviewed and graded on four-point severity scales for the following lesions of coal workers' pneumoconiosis (CWP): macules, micro- and macronodules (small and large fibrotic nodules), and progressive massive fibrosis (PMF). Antemortem CXR were classified by three B readers using the 1971 International Labor Office (ILO) U/C classification (6). On pathologic examination, 96% of miners had macules, 70% micronodules, 45% macronodules, 15% silicosis, and 28% PMF. By CXR, 69% of the miners had small, rounded opacity profusions of category > or = 0/1. Data analysis revealed increasing odds that small opacities of category > or = 0/1 would be detected with increasing grade of nodules. Profusion category 0/0 was often reported for cases with macules of mild to moderate grade and mild levels of micronodules. Overall, q-type opacities were associated with macules and micronodules, whereas the large r-type opacities were associated with macronodules. By CXR, large opacities showed good correlation with pathologic PMF. However, about one-third of cases identified as having large opacities by CXR were not substantiated as PMF by pathology. One-fourth of these cases could be explained by lung lesions such as Caplan's nodules, tuberculosis scars, and tumors. Similarly, 22% of cases classified as PMF on pathology had no large opacities by CXR. In half of these cases, the radiologists had noted other abnormalities (cancer, tuberculosis) by CXR as large opacities. Overall, the study showed good agreement (Somer's d = 0.64) between the predicted probabilities and observed responses of a profusion category > or = 0/1 for pathologic CWP lesions. However, the study also showed that CXR were insensitive for detecting minimal CWP lesions, and were unreliable indicators in the presence of concomitant pulmonary pathology.