tbuckley/cabot-search huggingface dataset:
The role of transgenic mouse models in carcinogen identification.
Authors: John B Pritchard, John E French, Barbara J Davis, Joseph K Haseman
Journal: Environmental Health Perspectives (2002)

In this article, we examine existing data on the use of transgenic mouse models for identification of human carcinogens. We focus on the three most extensively studied of these mice, Trp53+/-, Tg/AC, and RasH2, and compare their performance with the traditional 2-year rodent bioassay. Data on 99 chemicals were evaluated. Using the International Agency for Research on Cancer/Report on Carcinogens determinations for the carcinogenicity of these chemicals to humans as the standard for comparison, we evaluated a variety of potential testing strategies ranging from individual transgenic models to combinations of these three models with each other and with traditional rodent assays. The individual transgenic models made the "correct" determinations (positive for carcinogens; negative for noncarcinogens) for 74-81% of the chemicals, with an increase to as much as 83% using combined strategies (e.g., Trp53+/- for genotoxic chemicals and RasH2 for all chemicals). For comparison, identical analysis of chemicals in this data set that were tested in the 2-year, two-species rodent bioassay yielded correct determinations for 69% of the chemicals. However, although the transgenic models had a high percentage of correct determinations, they did miss a number of known or probable human carcinogens, whereas the bioassay missed none of these chemicals. Therefore, we also evaluated mixed strategies using transgenic models and the rat bioassay. These strategies yielded approximately 85% correct determinations, missed no carcinogens, and cut the number of positive determinations for human noncarcinogens in half. Overall, the transgenic models performed well, but important issues of validation and standardization need further attention to permit their regulatory acceptance and use in human risk assessment.
Internet Psycho-Education Programs Improve Outcomes in Youth With Type 1 Diabetes
Authors: Margaret Grey, Robin Whittemore, Sangchoon Jeon, Kathryn Murphy, Melissa S. Faulkner, Alan Delamater
Journal: Diabetes Care (2013)

The purpose of this study was to determine the efficacy of two Internet-based psycho-educational programs designed to improve outcomes for youth with type 1 diabetes transitioning to adolescence.The study was a multisite clinical trial of 320 youth (aged 11-14 years; 37% minority; 55% female) randomized to one of two Internet-based interventions: TeenCope or Managing Diabetes. Primary outcomes were HbA1c and quality of life (QOL). Secondary outcomes included coping, self-efficacy, social competence, self-management, and family conflict. Data were collected at baseline and after 3, 6, and 12 months online. Youth were invited to cross over to the other program after 12 months, and follow-up data were collected at 18 months. Analyses were based on mixed models using intent-to-treat and per-protocol procedures.Youth in both groups had stable QOL and minimal increases in HbA1c levels over 12 months, but there were no significant differences between the groups in primary outcomes. After 18 months, youth who completed both programs had lower HbA1c (P = 0.04); higher QOL (P = 0.02), social acceptance (P = 0.01), and self-efficacy (P = 0.03) and lower perceived stress (P = 0.02) and diabetes family conflict (P = 0.02) compared with those who completed only one program.Internet interventions for youth with type 1 diabetes transitioning to adolescence result in improved outcomes, but completion of both programs was better than only one, suggesting that these youth need both diabetes management education and behavioral interventions. Delivering these programs via the Internet represents an efficient way to reach youth and improve outcomes.
Doctors and Drugs
Authors: David C. Lewis
Journal: New England Journal of Medicine (1986)

We are now experiencing a high level of public concern about drug use and its consequences in our society. President Reagan has declared a war on drugs, which includes controversial proposals for widespread urine testing. Tougher sanctions have been instituted in regard to intoxicated behavior. The medical profession is being exhorted to improve the education of medical students, house staff, and practicing physicians about drug and alcohol abuse, to intensify research into the causes of drug use, abuse, and dependence, and to provide earlier intervention and better treatment for patients with alcoholism and drug abuse and for their families. Concurrently, . . .
INSULIN IN THE TREATMENT OF TUBERCULOSIS
Authors: FREDERICK M. ALLEN
Journal: JAMA (1933)

The work summarized in this paper comprises more than eighty nondiabetic tuberculosis cases. Several New York tuberculosis specialists kindly referred volunteers from their charity services to receive the first treatment in Morristown, and Eli Lilly &amp; Co., furnished insulin for this purpose. A preliminary announcement was previously published.<sup>1</sup>The observations were then extended in two parts, which will be published in detail in separate papers. One of these comprised a series of twenty-six cases studied in the Valley View Sanatorium, Paterson, N. J., in collaboration with Drs. William E. Pottinger, Stephen A. Douglas and Earl Warren. The second comprised forty-five cases observed in the City Hospital, Welfare Island, New York City, in collaboration with Dr. James S. Edlin. This work was a natural development from certain studies of diabetes. On the practical side, I<sup>2</sup>was apparently the first to publish observations on the use of insulin in diabetic
NOTES ON THE TREATMENT OF LICHEN PLANUS.
Authors: JOSEPH ZEISLER
Journal: JAMA (1903)

Intelligent treatment should be based, whenever possible, on a clear conception of the causes of disease. Etiology is bound to constitute, for many years to come, the most fruitful field for the student of dermatology, for at the present time it is but fair to confess that the essential nature of some of the most common diseases of the skin is very far from being clear to us. I need only refer to eczema, acne, psoriasis and pemphigus. Individual cases of these may admit of a satisfactory explanation; taken in their totality, we know precious little about their cause. The same holds true of lichen planus. The most complete treatises of the day are of a remarkable unanimity in admitting our ignorance as to its etiology. In preparing this paper I have carefully studied my private ease records for the past sixteen years. I have found notes of 71
Loss of desmoglein 1 associated with palmoplantar keratoderma, dermatitis and multiple allergies
Authors: C. Has, T. Jakob, Y. He, D. Kiritsi, I. Hausser, L. Bruckner-Tuderman
Journal: British Journal of Dermatology (2014)

Journal Article Loss of desmoglein 1 associated with palmoplantar keratoderma, dermatitis and multiple allergies Get access C. Has, C. Has Department of Dermatology Medical Center University of Freiburg Hauptstrasse 7 79104 Freiburg Germany Correspondence Cristina Has. E‐mail: cristina.has@uniklinik-freiburg.de Search for other works by this author on: Oxford Academic Google Scholar T. Jakob, T. Jakob Department of Dermatology Medical Center University of Freiburg Hauptstrasse 7 79104 Freiburg Germany Search for other works by this author on: Oxford Academic Google Scholar Y. He, Y. He Department of Dermatology Medical Center University of Freiburg Hauptstrasse 7 79104 Freiburg Germany Search for other works by this author on: Oxford Academic Google Scholar D. Kiritsi, D. Kiritsi Department of Dermatology Medical Center University of Freiburg Hauptstrasse 7 79104 Freiburg Germany Search for other works by this author on: Oxford Academic Google Scholar I. Hausser, I. Hausser Institute of Pathology University Clinic Heidelberg Heidelberg Germany Search for other works by this author on: Oxford Academic Google Scholar L. Bruckner‐Tuderman L. Bruckner‐Tuderman Department of Dermatology Medical Center University of Freiburg Hauptstrasse 7 79104 Freiburg Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 1, 1 January 2015, Pages 257–261, https://doi.org/10.1111/bjd.13247 Published: 01 January 2015
332. Routes of Ligand Administration That Give Efficient and Robust In Vivo Induction with the RheoSwitch® Therapeutic System
Authors: Marti A. DiPietro, Jessica L. Seitzer, David W. Potter
Journal: Molecular Therapy (2006)

The RheoSwitch® Therapeutic System (RTS) is used to regulate both the timing and level of gene expression in response to a systemically delivered small molecule ligand, Activator Drug. This inducible gene regulation system may have utility in human gene therapies that require a specifically regulated level of gene expression, where it is desirable to terminate the therapy when it is no longer needed, or where continuation of the therapy would be unsafe. The version of RTS used in these studies was comprised of an ecdysone receptor (EcR) fused to a GAL4 DNA binding domain, a chimeric retinoid X receptor fused to a VP16 activation domain (pVP16-Hs- LmRXR) , a human secreted alkaline phosphatase (hSEAP) reporter gene placed under the control of a 6xGAL4 response element, and a transthyretin minimal promoter (p6xGAL4-TTR-SEAP).
Increased expression of human T-cell immunoglobulin- and mucin-domain-containing molecule-4 in peripheral blood mononuclear cells from patients with system lupus erythematosus
Authors: Peiqing Zhao, Liyun Xu, Piming Wang, Xiaohong Liang, Jianni Qi, Peng Liu, Chun Guo, Lining Zhang, Chunhong Ma, Lifen Gao
Journal: Cellular and Molecular Immunology (2010)
Mortality from Pneumonia in Children in the United States, 1939 through 1996
Authors: Scott F. Dowell, Benjamin A. Kupronis, Elizabeth R. Zell, David K. Shay
Journal: New England Journal of Medicine (2000)

Pneumonia remains an important cause of childhood deaths throughout the world, but in developed countries, the mortality rate is decreasing. We reviewed death records for children in the United States from 1939 through 1996. A plot of the annual rates of change in the number of deaths from pneumonia was used to generate hypotheses about the influence of various events and interventions. We used data from the National Hospital Discharge Survey, the Medicaid program, and published reports to test these hypotheses.During the 58-year study period, the number of children who died from pneumonia declined by 97 percent, from 24,637 in 1939 to 800 in 1996. During the same period, the rate of mortality from other causes declined by 82 percent. There were steep declines in the mortality rates for pneumonia from 1944 to 1950, although the rate increased among older children in 1957, and there were sustained declines in all age groups from 1966 to 1982. From 1966 to 1982, the mortality declined by an average of 13.0 percent annually, and these decreases coincided with increases in the proportion of poor children covered by Medicaid, increases in rates of hospitalization for pneumonia, a narrowing of the gap between the mortality rate for black children and the rate for white children, and a convergence between the mortality rate in the South and the rates in the other three census regions.Since 1939, the rate of mortality from pneumonia in children in the United States has declined markedly. We hypothesize that the steep declines in the late 1940s are attributable to the use of penicillin, that the peak in 1957 was due to the influenza A pandemic, and that the sustained decline from 1966 through 1982 may be attributable in part to improved access to medical care for poor children.
Managing Anticoagulation Safely
Authors: Paulette Ginier
Journal: Annals of Internal Medicine (1993)

Letters1 November 1993Managing Anticoagulation SafelyPaulette Ginier, MD, Donald Tayloe, MD, and Suzanne Venturino, MDPaulette Ginier, MDSearch for more papers by this author, Donald Tayloe, MDSearch for more papers by this author, and Suzanne Venturino, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-9-199311010-00030 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In their recent article, Fihn and coworkers [1] state that because they found no seasonal variation in complication rate, ingestion of vegetables rich in vitamin K has little effect on the variability in prothrombin time ratio (PTR) [1]. However, three of the five study sites were on the West Coast where cruciferous vegetables are available year-round. In a similar setting (that is, an anticoagulation clinic with a defined protocol and an experienced practitioner), it is not uncommon, despite dietary instruction, for patients to have a subtherapeutic international normalized ratio (INR) that readily corrects when the vitamin-K content of their diet ...REFERENCE1. Fihn SD, McDonell M, Martin D, Henikoff J, Vermes D, Kent D, et al. Risk factors for complications of chronic anticoagulation: a multicenter study. Ann Intern Med. 1993; 118:511-20. Google Scholar Author, Article, and Disclosure InformationAuthors: Paulette Ginier, MD; Donald Tayloe, MD; Suzanne Venturino, MDAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1993Volume 119, Issue 9Page: 957KeywordsDietDrug therapyDrugsIngestionInternational normalized ratioProthrombin timeVitamin K ePublished: 15 August 2000 Issue Published: 1 November 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Expression of type IV collagen alpha 3 and alpha 4 chain mRNA in X-linked Alport syndrome.
Authors: K Nakanishi, N Yoskikawa, K Iijima, H Nakamura
Journal: Journal of the American Society of Nephrology (1996)

X-Linked Alport syndrome is caused by mutations in the COL4A5 gene encoding the Type IV collagen alpha 5 chain (alpha 5(IV)). The authors' recent immunohistochemical study demonstrated abnormal expression of alpha 3(IV) and alpha 4(IV), as well as of alpha 5(IV), in patients with this syndrome, and a correlation between abnormal alpha 3(IV) and alpha 4(IV) expression and severity of the disease. The mechanism linking alpha 5(IV) mutations with abnormal alpha 3(IV) and alpha 4(IV) expression is unknown. To examine alpha 3(IV) and alpha 4(IV) mRNA expression in renal cortical tissues of patients with X-linked Alport syndrome, a nonradioisotopic, semiquantitative reverse transcription-polymerase chain reaction assay (alpha 3(IV) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), alpha 4(IV), and GAPDH coamplification) was performed. There were no significant differences among severely affected male (N = 3), mildly affected male (N = 2), and female (N = 1) X-linked Alport patients and control subjects (N = 2) with respect to alpha 3(IV) and alpha 4(IV) mRNA expression in renal cortical tissue. These findings indicate that alpha 3(IV) and alpha 4(IV) transcription is not turned off in X-linked Alport syndrome and suggest that abnormal expression of alpha 3(IV) and alpha 4(IV) proteins in this syndrome may be the result of failure of incorporation of alpha 3(IV) and alpha 4(IV) into the glomerular basement membrane.
Maternal Anaesthetic Deaths
Authors: O. P. Dinnick
Journal: BMJ (1958)

MEtDICAL JOUWIULThis can only be done by cancer education of the public, which is largely a psychological problem.The nursing profession, who are the friends of the people and welcomed in their homes, are the best people to carry out such educa- tion.They can very easily be trained for the work, and the cost is almost infinitesimal.It does not interfere with their other duties, and is being done in York2 and one or two other areas, but why not in all ?-I am, etc., Oxford.
5-Hydroxytryptamine facilitates cholinergic bronchoconstriction in human and guinea pig airways.
Authors: T Takahashi, J K Ward, S Tadjkarimi, M H Yacoub, P J Barnes, M G Belvisi
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

5-hydroxytryptamine (5-HT) may not play a major role in controlling human airway smooth muscle tone, as it has little direct effect on airway caliber. However, its role as a neuromodulator has not been determined. We have identified a facilitatory effect of 5-HT on cholinergic neurotransmission and characterized the 5-HT receptors involved in human and guinea pig trachea. In guinea pig trachea, 5-HT facilitated electric field stimulation-induced cholinergic bronchoconstriction in a concentration-dependent manner (EC50 = 2.6 microM). The 5-HT3/4 and 5-HT3 antagonists, ICS 205-930 and ondansetron, inhibited the effect of 5-HT competitively (pA2 values of 7.3 and 7.1, respectively); methiothepin (5-HT1/2C antagonist), ketanserin (5-HT2A antagonist), and GR 113808A (5-HT4 antagonist) had no effect. The rank order of potency of 5-HT agonists was 5-HT > 2-methyl-5-HT (5-HT3 selective) > 5-methoxytryptamine (5-HT4 selective) > alpha-methyl-5-HT (5-HT2 selective). 5-carboxamidotryptamine (5-HT1A/B/D) and sumatriptan (5-HT1D selective) were essentially inactive. 5-Hydroxytryptamine had no effect on contractile responses to exogenous acetylcholine, suggesting that 5-HT facilitates cholinergic bronchoconstriction via prejunctional receptors. In human bronchi, 5-HT also facilitated cholinergic bronchoconstriction, which was inhibited by ICS 205-930. The effects of the 5-HT3 antagonists and selective agonists in human and guinea pig airways suggests that these facilitatory effects are mediated by 5-HT3 receptors.
Retracted: RhoA activation and interaction with Caveolin-1 are critical for pressure-induced myogenic tone in rat mesenteric resistance arteries
Authors: Caroline Dubroca, Xavier Loyer, Kevin Retailleau, Gervaise Loirand, Pierre Pacaud, Olivier Feron, Jean-Luc Balligand, Bernard I. Lévy, Christophe Heymes, Daniel Henrion
Journal: Cardiovascular Research (2006)

Myogenic tone, which has a major role in the regulation of local blood flow, refers to the ability of vascular smooth muscle to adapt its contractility to changes in transmural pressure. Although Rho-kinase is involved in myogenic tone, the pathway involved remains unclear, especially concerning translocation to the plasma membrane and activation of RhoA. As caveolae have a key role in the signal transduction of membrane-bound proteins, we tested the hypothesis that RhoA might be activated by pressure and that its activation might involve caveolin-1, which has been shown to be involved in vascular functions.Myogenic tone was studied in isolated rat mesenteric resistance arteries (118+/-15 microm internal diameter with a pressure of 75 mmHg) submitted to pressure steps (25, 75, and 150 mmHg). Pharmacological blockade of caveolae or RhoA-Rho-kinase pathway was assessed by confocal microscopy in pressurized arteries to analyze protein co-localization and by co-immunoprecipitation in order to confirm protein interactions. Caveolin-1-deficient mice were used to confirm the role of the protein in myogenic tone.Pressure-induced myogenic tone was significantly reduced by RhoA inactivation with TAT-C3 (90.5% inhibition at 150 mmHg) and by the Rho-kinase inhibitor Y27632 (91.8% inhibition at 150 mmHg). In arteries pressurized at 150 mmHg, RhoA was localized to the plasma membrane (localization by confocal microscopy and increased quantity of RhoA in the membrane fraction after protein extraction). Thus, translocation of RhoA to the plasma membrane was associated with pressure-induced tone. In addition, caveolae disruption with methyl-beta-cyclodextrin reduced myogenic tone by 66% at 150 mmHg. Further, myogenic tone was significantly reduced to 24% of control in caveolin-1-deficient mice (active tone was 32.3+/-2.8 microm and 9.1+/-3.7 microm in +/+ and -/- mice, respectively, n = 5 per group), suggesting a key role of caveolin-1 in myogenic tone. Finally, RhoA and caveolin-1 co-immunoprecipitation and co-localization significantly increased when myogenic tone developed at 150 mmHg (co-localization showed 26+/-13% merging at 25 mmHg versus 97+/-21% at 150 mmHg, n = 5). Co-immunoprecipitation was prevented by TAT-C3 and by methyl beta-cyclodextrin.RhoA activation is critical for the development of myogenic tone in resistance arteries. This activation induced translocation of RhoA to the plasma membrane within caveolae, where the interaction of RhoA with caveolin-1 leads selectively to the activation of a Rho-kinase-dependent force development.
Brain biocompatibility of a biodegradable controlled release polymer consisting of anhydride copolymer of fatty acid dimer and sebacic acid
Authors: Henry Brem, Abraham Domb, Doris Lenartz, Catalino Dureza, Alessandro Olivi, Jonathan I. Epstein
Journal: Journal of Controlled Release (1992)

The development of new biodegradable polymers (e.g. PCPP-SA) has allowed the prolonged controlled release of lipid soluble chemotherapeutic agents in the laboratory and clinically. In order to optimize this approach, a new polymer has been developed (the copolymer of fatty acid dimer and sebacic acid p[FAD-SA]) to release water soluble agents. In this study we sought to determine the safety and biocompatibility of this new polymer in the brain. We compared the tissue reaction to this polymer to the reaction observed with oxidized cellulose (SurgicelR) and with absorbable gelatin sponge (GelfoamR). Fifty-six adult Fischer 344 rats were assigned to 1 of 7 groups and underwent bilateral 3 mm burr holes. Neurological or behavioral changes were assessed daily and the groups were killed sequentially on postoperative days 3, 6, 10, 15, 21, 28, and 36. No neurological deficits or behavioral changes suggestive of either systemic or localized toxicity were observed in the animals implanted with the new polyanhydride. A well demarcated acute inflammatory response was seen at day 3 and 6 for p(FAD-SA) and SurgicelR implants. The inflammatory response remained well localized and resolved with total degradation of the polymer by day 36. The localized reaction evoked by this polymer was comparable to the one of the previously studied biodegradable polymers (PCPP-SA) and to the response to commonly used surgical hemostatic materials such as SurgicelR. The biodegradable copolymer of fatty acid dimer and sebacic acid may play an important role in drug delivery to the brain by by-passing the blood-brain barrier to administer water soluble agents directly to the brain.