tbuckley/cabot-search huggingface dataset:
Mouse Double Minute 2 Associates with Chromatin in the Presence of p53 and Is Released to Facilitate Activation of Transcription
Authors: David E. White, Kathryn E. Talbott, Nicoleta C. Arva, Jill Bargonetti
Journal: Cancer Research (2006)

Abstract The tumor suppressor p53 is a potent transcription factor of which the ability to mediate transcription is inhibited through an interaction with the oncoprotein mouse double minute 2 (Mdm2). The present study has tested the hypothesis that Mdm2 inhibits the p53 response in normally growing cells by binding to chromatin-associated p53. Using chromatin immunoprecipitation, we show that Mdm2 localizes with p53 at its responsive elements on the waf1 and mdm2 genes in human cell lines expressing p53, but not in cell lines lacking p53 expression, indicating that Mdm2 is recruited to regions of DNA in a p53-dependent manner. Interestingly, our results show a decrease of Mdm2 protein associated with p53-responsive elements on the waf1 and mdm2 genes when p53-induced transcription is activated either by DNA damage or through controlled overexpression of p53. Rapid activation of p53 transcriptional activity before increasing p53 protein levels was observed with addition of either small-molecule inhibitors to disrupt the p53-Mdm2 interaction or small interfering RNA to mdm2. These findings indicate Mdm2 transiently localizes with p53 at responsive elements and suggest that latent p53 results from the recruitment of Mdm2 to chromatin. (Cancer Res 2006; 66(7): 3463-70)
Recurrent vasculitis associated with beta-haemolytic streptococcal infections.
Authors: S B Lucas, J Moxham
Journal: BMJ (1978)

Recurrent vasculitis associated with beta-haemolytic streptococcal infectionsMany agents have been incriminated in producing polyarteritis nodosa and similar systemic vasculitic disorders, including the hepatitis B virus' and various drugs.2 3 We report a case in which recurrent episodes of severe systemic vasculitis were associated with haemolytic streptococcal infections. Case reportIn 1968, when aged 17 years, the patient developed a sore throat, which worsened over four weeks despite treatment with penicillin and tetracycline.On admission to hospital she was very ill, with fever, facial oedema, swollen tongue, tender muscles, and bilateral lateral popliteal nerve palsies.A few days later she developed polyarthritis and red papules on the hands and feet.Further treatment with tetracycline, ampicillin, and erythromycin was unhelpful.Investigations showed a white cell count of 23 x 109/1 (82% -neutrophils, no eosinophils), ESR 77 mm in first hour, and ASO titre 230 (normal < 200), and a throat swab cultured Streptococcus pyogenes.Histo- logically a skin biopsy specimen showed an intense arteritis.Hydrocortisone and azathioprine produced dramatic clinical improvement; after six months this was stopped and by 18 months her foot drop had resolved leaving her completely well.She again acquired a severe sore throat in February 1977; despite treat- ment with erythromycin, and later tetracycline, she deteriorated and was readmitted with fever; facial oedema; gross swelling and ulceration of the tongue (see figure); painful muscles; a maculopapular rash over the buttocks; Swelling and ulceration of tongue.radial, median, and lateral popliteal nerve palsies; and necrosis of the soft
Abstract 1247: Assessment of the roles of prostaglandin E2 receptors in a rodent model of chemically induced esophageal carcinogenesis
Authors: Ni Shi, Tong Chen
Journal: Cancer Research (2014)

Abstract Esophageal carcinogenesis is a multistage process characterized by morphological changes from normal esophagus to basal cell hyperplasia, dysplasia, carcinoma in situ and squamous cell carcinoma (SCC). Our laboratory has used a rodent model of N-nitrosomethylbenzylamine (NMBA)-induced esophageal SCC to investigate molecular carcinogenesis and identify putative chemopreventive agents. In our previous studies, we found that the expression of cyclooxygenase-2 and the production of prostaglandin E2 (PGE2) in rat esophageal epithelium were elevated in papillomatous lesions relative to precancerous and normal tissues. PGE2 exerts its cellular effect by binding to its cognate receptors. There are four subtypes of PGE2 receptors, EP1, EP2, EP3 and EP4, which are involved in carcinogenesis depending on the cell or tissue types. The overall objective of the current study was to assess the roles of PGE2 receptors in NMBA-induced rat esophageal tumorigenesis. F344 rats were injected subcutaneously with NMBA (0.30 mg/kg b.w.) three times per week for five weeks. One week after NMBA treatment, animals were randomized into five experimental groups and fed 300 ppm celcecoxib plus 50 ppm S,S'-1,4-phenylenebis(1,2-ethanediyl)bisisothiourea (PBIT) starting from week 6, 9, 12 , or 15, respectively, or 5% freeze-dried black raspberries (BRB) starting from week 6. Esophagi were collected at 29 weeks. Results of real-time PCR, western blot analysis and immunohistochemistry demonstrated a correlation between the upregulation of EP1, EP2, EP3 and EP4 and neoplastic progression in the rat esophagus. The expression of the PGE2 receptors in preneoplastic tissues and papillomas was significantly elevated when compared to normal tissues. Moreover, we observed that celecoxib + PBIT and 5% BRB significantly reduced EP2 expression. Our data suggest, therefore, that the production of PGE2 receptors by the esophageal epithelium is associated with the development of NMBA-induced esophageal tumorigenesis in rats, and EP2 antagonist may have chemopreventive potential in esophageal cancer. Research efforts are needed to elucidate the function of PGE2 receptors and related oncogenic pathways in esophageal SCC. (Supported by NIH/NCI R01 CA131073-01A1). Citation Format: Ni Shi, Tong Chen. Assessment of the roles of prostaglandin E2 receptors in a rodent model of chemically induced esophageal carcinogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1247. doi:10.1158/1538-7445.AM2014-1247
CD39 EXPRESSION MODULATES ISCHEMIA INDUCED DIASTOLIC DYSFUNCTION
Authors: Zhaobin Xu, Sibel Gokce, Shouvik D. Mahamud, Debra G. Wheeler, Karen M. Dwyer, Anthony J.F. d&apos;Apice, Simon C. Robson, Peter J. Cowan, Richard J. Gumina
Journal: Journal of the American College of Cardiology (2012)
Kerion masquerading as erosive pustular dermatosis of the scalp
Authors: A.J.G. McDonagh, S.S. Bleehen
Journal: British Journal of Dermatology (1991)

Journal Article Kerion masquerading as erosive pustular dermatosis of the scalp Get access A.J.G. McDonagh, A.J.G. McDonagh Department of Dermatology, Royal Hallamshire Hospital, Sheffield S10 2JP, U.K. Search for other works by this author on: Oxford Academic Google Scholar S.S. Bleehen S.S. Bleehen Department of Dermatology, Royal Hallamshire Hospital, Sheffield S10 2JP, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 124, Issue 5, 1 May 1991, Pages 507–508, https://doi.org/10.1111/j.1365-2133.1991.tb00640.x Published: 01 May 1991
The Molecular Basis of Gonadotropin-Releasing Hormone Action*
Authors: P. MICHAEL CONN
Journal: Endocrine Reviews (1986)

WE HAVE known for more than 15 yr that release of the pituitary gonadotropins (LH and FSH) is regulated by a decapeptide from the hypothalamus, GnRH. This releasing hormone is active in vivo, as well as in pituitary explants, and in cell cultures. Accordingly, it has been possible to obtain a great deal of data which have been used to develop an understanding of GnRH action at the cellular level. Models of GnRH action have been useful to understand and predict the actions of GnRH in vivo and to design means for using the releasing hormone in the treatment of human disorders. The present review will describe our current understanding of GnRH action and serve to update our previous review in this series (1).
Studies on the mechanism of 1,3-butadiene-induced leukemogenesis: the potential role of endogenous murine leukemia virus.
Authors: R D Irons
Journal: Environmental Health Perspectives (1990)

Previous studies have revealed marked differences in the incidence of leukemia between rats and mice exposed to 1,3-butadiene that do not appear to be readily explained on the basis of pharmacokinetics or metabolism. Chronic exposure to 1,3-butadiene results in a high incidence of thymic lymphoma in B6C3F1 mice that is not observed in Sprague-Dawley rats. Studies at the Chemical Industry Institute of Toxicology have focused on evaluating the potential of endogenous ecotropic retroviral background to influence susceptibility to 1,3-butadiene leukemogenesis. These studies have compared the pathogenesis and incidence of thymic lymphoma between B6C3F1 and NIH Swiss mice. Proviral ecotropic sequences are truncated in the NIH Swiss mouse, and the virus is not expressed. Chronic exposure to 1,3-butadiene (1250 ppm) for up to 1 year resulted in a fourfold difference in the incidence of thymic lymphoma between B6C3F1 and NIH Swiss mice. These results provide presumptive evidence for retrovirus involvement since NIH Swiss mice lack ecotropic viruses and appear to be relatively resistant to induction of lymphoma by 1,3-butadiene. Other explanations appear to be less likely in light of the fact that target organ toxicity has been determined to be virtually identical between the two strains during the preleukemic phase of 1,3-butadiene exposure.
Re-evaluating the efficacy of β-adrenergic agonists and antagonists in long QT-3 syndrome through computational modelling
Authors: Rebecca C. Ahrens-Nicklas, Colleen E. Clancy, David J. Christini
Journal: Cardiovascular Research (2009)

Long QT syndrome (LQTS) is a heterogeneous collection of inherited cardiac ion channelopathies characterized by a prolonged electrocardiogram QT interval and increased risk of sudden cardiac death. Beta-adrenergic blockers are the mainstay of treatment for LQTS. While their efficacy has been demonstrated in LQTS patients harbouring potassium channel mutations, studies of beta-blockers in subtype 3 (LQT3), which is caused by sodium channel mutations, have produced ambiguous results. In this modelling study, we explore the effects of beta-adrenergic drugs on the LQT3 phenotype. In order to investigate the effects of beta-adrenergic activity and to identify sources of ambiguity in earlier studies, we developed a computational model incorporating the effects of beta-agonists and beta-blockers into an LQT3 mutant guinea pig ventricular myocyte model. Beta-activation suppressed two arrhythmogenic phenomena, transmural dispersion of repolarization and early after depolarizations, in a dose-dependent manner. However, the ability of beta-activation to prevent cardiac conduction block was pacing-rate-dependent. Low-dose beta-blockade by propranolol reversed the beneficial effects of beta-activation, while high dose (which has off-target sodium channel effects) decreased arrhythmia susceptibility. These results demonstrate that beta-activation may be protective in LQT3 and help to reconcile seemingly conflicting results from different experimental models. They also highlight the need for well-controlled clinical investigations re-evaluating the use of beta-blockers in LQT3 patients.
Phase II Randomized Study of Dose-Dense Docetaxel and Cisplatin Every 2 Weeks With Pegfilgrastim and Darbepoetin Alfa With and Without the Chemoprotector BNP7787 in Patients With Advanced Non-small Cell Lung Cancer (CALGB 30303)
Authors: Antonius A. Miller, Xiaofei F. Wang, Lin Gu, Philip Hoffman, Jamil Khatri, Frank Dunphy, Martin J. Edelman, Michael Bolger, Everett E. Vokes, Mark R. Green
Journal: Journal of Thoracic Oncology (2008)
Foxp3 Transcription Factor Is Proapoptotic and Lethal to Developing Regulatory T Cells unless Counterbalanced by Cytokine Survival Signals
Authors: Xuguang Tai, Batu Erman, Amala Alag, Jie Mu, Motoko Kimura, Gil Katz, Terry Guinter, Tom McCaughtry, Ruth Etzensperger, Lionel Feigenbaum, Dinah S. Singer, Alfred Singer
Journal: Immunity (2013)
ENDEMIC CEREBROSPINAL FEVER IN CHILDHOOD
Authors: E. B. SHAW
Journal: JAMA (1933)

Infections of the central nervous system in childhood present a fascinating part of pediatric practice. Among these, cerebrospinal fever is of especial interest in that it constitutes an acute medical condition not unlike the acute surgical emergencies. During epidemics of the disease, when apprehension stimulates diagnostic acuity, early forms of infection are recognized which are commonly believed to characterize the epidemic form. Although Herrick,<sup>1</sup>Netter and Salanier<sup>2</sup>and others stated that sporadic cases frequently reveal typical early symptoms, the diagnosis in these cases is commonly not made until evidences of meningitis appear. Many observers accordingly describe an experience with sporadic cases which is limited mostly to the meningitic stage and restrict discussion to this stage of final localization. A series of fifty-eight consecutive cases of cerebrospinal fever in children admitted to the Children's Hospital, San Francisco, during the past ten years, presents unusual prominence of signs of systemic
The Prediction of Immunity to Coronary Heart Disease
Authors: Ray H. Rosenman
Journal: JAMA (1966)

The occurrence of new coronary heart disease (CHD) in the presence of below average serum levels of lipids and lipoproteins was studied during a 4 1/2-year period of observation of 2,998 normotensive men, aged 39 to 59 years at intake into a prospective, epidemiological investigation. It was found from this study that the normotensive, middle-aged man with the<i>fully developed</i>type B behavior pattern was essentially immune to the development of clinical CHD if he exhibited a serum cholesterol level less than 226 mg/100 ml, a serum triglyceride level less than 126 mg/100 ml, or a serum β-/α-lipoprotein ratio less than 2.01, singly or in combination.
Prejudice against women doctors.
Authors: F Lefford
Journal: BMJ (1987)

Prejudice against doctors and students from ethnic minorities SIR,-As Dr Richard Smith states (7 February, p 328), doctors trained overseas have been dis- advantaged in competing for jobs in the National Health Service.The study by Smith in 1980 proved this beyond any measure of doubt.'The profession's concern about the competence of many such doctors led to the recommendations of the Merrison Committee, in 1975, which required a substantial proportion ofoverseas doctors to take the Professional and Linguistic Assessment Board examination (PLAB), a test of professional com- petence at the level of senior house officer and of formal and colloquial English.
Dynamin-2 Regulates Oxidized Low-Density Lipoprotein–Induced Apoptosis of Vascular Smooth Muscle Cell
Authors: Yuji Kashiwakura, Masami Watanabe, Norihiro Kusumi, Katsuhiko Sumiyoshi, Yasutomo Nasu, Hiroshi Yamada, Tatsuya Sawamura, Hiromi Kumon, Kohji Takei, Hiroyuki Daida
Journal: Circulation (2004)

On exposure to oxidized low-density lipoprotein (oxLDL), vascular cells generally undergo apoptosis, which is one of the major pathogenic factors of atherosclerosis. In this study, we examined the role of dynamin (a crucial GTPase protein in endocytosis) in oxLDL-induced apoptosis of vascular smooth muscle cells (VSMC).After oxLDL stimulation, dynamin-2 colocalized with LOX-1 around the cell surface, as well as oxLDL in the cytoplasm, suggesting that dynamin-2 was involved in scavenger receptor-mediated oxLDL endocytosis. Downregulation of dynamin-2 induced by dynamin-2 dominant negative plasmid (K44A) resulted in a decrease of oxLDL uptake and thereby in a reduction of apoptosis. These data demonstrated that dynamin-2 was involved in oxLDL-induced apoptosis via the oxLDL endocytotic pathway. On the other hand, dynamin-2 wild-type plasmid transfection promoted oxLDL-induced apoptosis without increasing oxLDL uptake. Interestingly, the p53 inhibitor pifithrin-alpha (PFT) significantly reduced apoptosis promoted by wild-type dynamin-2 (78% reduction compared with the PFT[-] condition). These results indicated that dynamin-2 enhanced oxLDL-induced apoptosis of VSMC by participating in the p53 pathway, probably as a signal transducer. Moreover, we demonstrated that, in advanced plaques of apolipoprotein E-/- mice, dynamin-2 expression was often enhanced in apoptotic VSMC, suggesting that dynamin-2 might participate in apoptosis of VSMC even in vivo.Our data demonstrated that dynamin-2 at least partially regulated oxLDL-induced apoptosis of VSMC by participating in 2 independent pathways: the oxLDL endocytotic pathway and the p53 pathway. These findings suggest that dynamin-2 may serve as a new research or therapeutic target in vascular disease.
Five-Gene Model to Predict Survival in Mantle-Cell Lymphoma Using Frozen or Formalin-Fixed, Paraffin-Embedded Tissue
Authors: Elena Hartmann, Verònica Fernàndez, Victor Moreno, Joan Valls, Luis Hernández, Francesc Bosch, Pau Abrisqueta, Wolfram Klapper, Martin Dreyling, Eva Hoster, Hans Konrad Müller-Hermelink, German Ott, Andreas Rosenwald, Elías Campo
Journal: Journal of Clinical Oncology (2008)

Despite the common underlying translocation t(11;14) involving cyclin D1 that is present in nearly all cases of mantle-cell lymphoma (MCL), the clinical course of the disease is highly variable. The aim of the present study was to develop a quantitative gene expression-based model to predict survival in newly diagnosed patients with MCL that involves a minimum number of genes and is applicable to fresh-frozen and formalin-fixed, paraffin-embedded (FFPE) tumor samples.The expression of 33 genes with potential prognostic and pathogenetic impact in MCL was analyzed using quantitative reverse-transcription polymerase chain reactions (qRT-PCR) in a low-density array format in frozen tumor samples from 73 patients with MCL. Multivariate Cox methods and stepwise algorithms were applied to build gene expression-based survival predictors. An optimized five-gene model was subsequently applied to FFPE tumor samples from 13 patients with MCL from the initial series and to 42 independent MCL samples.The optimized survival predictor was composed of the five genes RAN, MYC, TNFRSF10B, POLE2, and SLC29A2 and was validated for application in FFPE tissue samples. It allowed the survival prediction of patients with MCL with widely disparate clinical outcome and was superior to the immunohistochemical marker Ki-67, an established prognostic factor in MCL.We here present a validated qRT-PCR-based test for survival prediction in patients with MCL that is applicable to fresh frozen as well as to FFPE tissue specimens. This test may prove useful to guide individualized treatment approaches for patients with MCL.
Measurement of radiographic changes occurring in rheumatoid arthritis by image analysis techniques.
Authors: P.A Gaydecki, M Browne, H Mamtora, D.M Grennan
Journal: Annals of the Rheumatic Diseases (1987)

We have applied image analysis techniques to serial measurements of bone contour in standard radiographs of single small joints of the hands in subjects with rheumatoid arthritis (RA) and controls. Adequate reproducibility was shown in 20 controls radiographed twice over a six month period. The technique showed significant changes in a proximal interphalangeal joint of 13 of 15 patients with RA studied over periods of three to 10 months. In further serial studies in selected small joints of RA hands significant changes could be shown as early as four months. These results justify further development of these techniques to allow their full scale evaluation in multiple joints in patients with RA receiving long term drug therapy.
Impact of Malignant Disease on the General Practitioner
Authors: R. Gibson
Journal: BMJ (1964)

My brief, I think, is to describe the impact of malignant disease on the general practitioner." Impact" is, according to the dictionary, " collision or sudden, violent encounter."What is required of me, therefore, is to describe the impression produced on the G.P. when he meets a patient with malignant disease, and the clash of conflicting interests between the doctor and the disease-the one bent on prolonging life, the other on destroying it.
Mitochondrial gene order is not conserved in arthropods: prostriate and metastriate tick mitochondrial genomes
Authors: W. C. Black, R. L. Roehrdanz
Journal: Molecular Biology and Evolution (1998)

The entire mitochondrial genome was sequenced in a prostriate tick, Ixodes hexagonus, and a metastriate tick, Rhipicephalus sanguineus. Both genomes encode 22 tRNAs, 13 proteins, and two ribosomal RNAs. Prostriate ticks are basal members of Ixodidae and have the same gene order as Limulus polyphemus. In contrast, in R. sanguineus, a block of genes encoding NADH dehydrogenase subunit 1 (ND1), tRNA(Leu)(UUR), tRNA(Leu)(CUN), 16S rDNA, tRNA(Val), 12S rDNA, the control region, and the tRNA(Ile) and tRNA(Gln) have translocated to a position between the tRNA(Glu) and tRNA(Phe) genes. The tRNA(Cys) gene has translocated between the control region and the tRNA(Met) gene, and the tRNA(Leu)(CUN) gene has translocated between the tRNA(Ser)(UCN) gene and the control region. Furthermore, the control region is duplicated, and both copies undergo concerted evolution. Primers that flank these rearrangements confirm that this gene order is conserved in all metastriate ticks examined. Correspondence analysis of amino acid and codon use in the two ticks and in nine other arthropod mitochondrial genomes indicate a strong bias in R. sanguineus towards amino acids encoded by AT-rich codons.
The Impact of College Prematriculation Immunization Requirements on Risk for Measles Outbreaks
Authors: A L Baughman, W W Williams, W L Atkinson, L G Cook, M Collins
Journal: JAMA (1994)

To assess whether prematriculation immunization requirements (PIRs) affect the number of measles cases on college campuses.We surveyed a stratified random sample of 880 colleges and universities to determine their immunization policies and practices and occurrence of measles outbreaks from 1988 through 1991. We merged national measles surveillance data with survey data by county to determine the risk for measles introduction on college campuses. We used logistic regression methods to estimate the effect of PIRs and assess risk factors for college measles outbreaks.A total of 3205 US colleges and universities listed in standard guides.Of selected schools, 91 (11%) of the 796 responding schools reported one or more measles cases occurring from 1988 through 1991. Schools with a state-mandated PIR were significantly less likely to report measles outbreaks of two or more cases than other institutions (adjusted relative risk [RR] = 0.30; 95% confidence interval [Cl], 0.11 to 0.84). None of the 14 schools that reported outbreaks of 10 or more cases was subject to state regulation or had a PIR specifying two doses of measles vaccine in place. Of schools with introduction of measles, residential colleges were more likely to report extensive spread of measles (five or more cases) than nonresidential colleges (RR = 35.8; 95% Cl, 2.08 to 617.0). Of public schools, 4-year programs had a higher risk of a large outbreak (five or more cases) than 2-year programs.These results strongly support current recommendations for requiring proof of vaccination of college students to decrease the risk for measles outbreaks on college campuses. State regulations mandating PIRs ensure the best protection against widespread measles transmission.