tbuckley/cabot-search huggingface dataset:
Multiple epidermoid cysts in Darier's disease
Authors: N. Nabeshima, M. Kumakiri, A. Ohkawara
Journal: British Journal of Dermatology (1996)

Journal Article Multiple epidermoid cysts in Darier's disease Get access N. Nabeshima, N. Nabeshima Department of Dermatology Hokkaido University School oj Medicine, Kita 15‐Jo, Nishi 7‐Chome, Kita‐ku, Sapporo, 060, Japan Search for other works by this author on: Oxford Academic Google Scholar M. Kumakiri, M. Kumakiri Department of Dermatology Hokkaido University School oj Medicine, Kita 15‐Jo, Nishi 7‐Chome, Kita‐ku, Sapporo, 060, Japan Search for other works by this author on: Oxford Academic Google Scholar A. Ohkawara A. Ohkawara Department of Dermatology Hokkaido University School oj Medicine, Kita 15‐Jo, Nishi 7‐Chome, Kita‐ku, Sapporo, 060, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 134, Issue 6, 1 June 1996, Pages 1163–1164, https://doi.org/10.1111/j.1365-2133.1996.tb07976.x Published: 01 June 1996
Abstract 5486: Combined targeting of the PI3K and MAPK pathways is required for efficacy in treating colorectal cancer of the wild and mutant types
Authors: Seung-Woo Hong, Jae-Sik Shin, Dong-Hoon Jin, Yong-Sang Hong, Jae-Lyun Lee, Min-Hee Ryu, Tae-Won Kim
Journal: Cancer Research (2011)

Abstract The KRAS oncogene is commonly mutated in human colon cancer. The downstream pathways of mutant KRAS, including the RAF/MEK/ERK, mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K)-AKT signaling are indispensible in order to understand how to pharmacologically target them when treating colon cancer with the KRAS mutant. However, the heterogeneous responses of these effector pathways remain unclear. Recent studies have indicated that mutational activation of PI3K (PIK3CA) in KRAS mutant tumor cells induces resistance to the inhibition of MEK, one of the MAPK signal cascades. Wild-type p53 also suppresses the oncogenic potential of the MAPK pathway. Our study shows that bortezomib inhibits the PI3K-AKT pathway and that nutlin-3A used as a p53-inducing agent blocks the MAPK pathway. The high doses of bortezomib induced apoptosis through complete suppression of AKT phosphorylation in KRAS and PI3K mutant colon cancer cells. Treating patients using high doses of nutlin-3A resulted in apoptosis by inducing p53 phosphorylation in colon cancer cells with wild-type p53. We also showed that the combination of bortezomib and nutlin-3A exhibited a synergistic effect on KRAS mutant colon cancer cells with PI3K mutant and wild-type p53, whereas there are no combined effect in KRAS mutant colon cancer cells with the p53 mutant. In addition, bortezomib and nutlin-3A exhibited combined effect in KRAS wild-type colon cancer cells with PI3K mutant and wild-type p53, although not in p53 mutant cells. We consistently noted that treatment with bortezomib and nutlin-3A after p53 silencing using small, interfering RNA (siRNA) in p53 wild-type colon cancer cells, resulted in a decrease of the populations of dead cells. Therefore, these results suggest that a combination of bortezomib and nutlin-3A can overcome the heterogeneous responses of the effector pathway in colon cancer with KRAS mutant; they also provide a new basis for the clinical testing of PI3K- and MAPK-targeted therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5486. doi:10.1158/1538-7445.AM2011-5486
777 PRECLINICAL CHARACTERIZATION OF NON-COVALENT HCV NS3/4A PROTEASE INHIBITOR BI 201335
Authors: P.W. White, M. Llinas-Brunet, M. Amad, G. Bolger, M.G. Cordingley, J. Duan, M. Garneau, L. Lagace, D. Thibeault, G. Kukolj
Journal: Journal of Hepatology (2010)
PHAGOCYTOSIS IN SUBACUTE BACTERIAL ENDOCARDITIS
Authors: Paul G. Quie, Ronald P. Messner, Ralph C. Williams
Journal: The Journal of Experimental Medicine (1968)

The opsonic properties of immune gammaG-globulins isolated from patients with chronic septicemic conditions, principally subacute bacterial endocarditis were studied. Opsonic capacity as well as complement-fixing properties of gamma-globulins appeared to be closely associated with integrity of Fc structures. Progressive pepsin digestion of immune gammaG-globulins, as monitored by successive loss of Gm(a) and Gm(b) antigens, abolished opsonic activity. Colostral gammaA, containing agglutinating antibacterial antibodies but no demonstrable complement-fixing activity, was devoid of opsonic capacity. Reduction of gamma-globulin opsonins with 0.01 or 0.1 M mercaptoethanol progressively abolished opsonic activity in parallel with loss of ability of treated gamma-globulins to fix complement with bacteria. Treatment of gamma-globulin opsonins with 0.01 M sodium metaperiodate also produced complete loss of opsonic capacity in parallel with loss of Gm(b) Fc antigens. These findings, together with antiopsonic effects demonstrable with anti-gamma-globulin factors showing primary reactivity with Fc structures, indicate that the opsonic property of immune gamma-globulins requires the participation of structures integral to the Fc region of gamma-globulin.
Wilson's Disease: Disseminated Intravascular Coagulation?
Authors: ALAN FEINER
Journal: Annals of Internal Medicine (1977)

Comments1 June 1977Wilson's Disease: Disseminated Intravascular Coagulation?ALAN FEINER, M.D.ALAN FEINER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-86-6-831_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I found the recent paper by Roche-Sicot and Benhamou (Ann Intern Med 86:301-303, 1977) interesting. However, in reading the case reports, I wondered how disseminated intravascular coagulation was excluded as an explanation for the intravascular hemolysis and hypoprothrombinemia.The occurrence of disseminated intravascular coagulation with tissue necrosis is recognized (1), and its association with hepatotoxicity is known (2)....References1. WINTROBE M: Clinical Hematology. Philadelphia, Lea & Feliger, 1974, p. 1213 Google Scholar2. SBARBAROBENNETT JR: Aspirin hepatotoxicity and disseminated intravascular coagulation. Ann Intern Med 86:183-185, 1977 LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: University of Colorado Medical Center 4200 E. 9th Avenue Denver, CO 80220 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1977Volume 86, Issue 6Page: 831-831KeywordsDisseminated intravascular coagulationMetastasisNecrosis Issue Published: 1 June 1977 PDF downloadLoading ...
Placental Transfer of Conjugated Bisphenol A and Subsequent Reactivation in the Rat Fetus
Authors: Miyu Nishikawa, Hidetomo Iwano, Risa Yanagisawa, Nanako Koike, Hiroki Inoue, Hiroshi Yokota
Journal: Environmental Health Perspectives (2010)

BackgroundBisphenol A (BPA), a well-known endocrine disruptor, is highly glucuronidated in the liver, and the resultant BPA-glucuronide (BPA-GA) is excreted primarily into bile. However, in rodents, prenatal exposure to low doses of BPA can adversely affect the fetus, despite the efficient drug-metabolizing systems of the dams. The transport mechanisms of BPA from mother to fetus are unknown.ObjectivesTo test our hypothesis that BPA-GA—an inactive metabolite—is passed through the placenta to the fetus, where it affects the fetus after reactivation, we investigated the placental transfer of BPA-GA and reactivation to BPA in the fetus.MethodsAfter performing uterine perfusion with BPA-GA in pregnant rats, we examined the expression and localization of the placental transporters for drug metabolites in the perfusate by reverse-transcriptase polymerase chain reaction and immunohistochemistry. We also investigated the deconjugation of BPA-GA in the fetus and examined uridine 5′-diphospho-glucuronosyltransferase (UGT) activity toward BPA and the expression of UGT isoforms in fetal liver.ResultsWe detected BPA-GA and deconjugated BPA in the fetus and amniotic fluid after perfusion. In the trophoblast cells, organic anion-transporting polypeptide 4a1 (Oatp4a1) was localized on the apical membrane, and multidrug resistance-associated protein 1 (Mrp1) was localized to the basolateral membrane. We observed deconjugation of BPA-GA in the fetus; furthermore, we found the expression of UGT2B1, which metabolizes BPA, to be quite low in the fetus.ConclusionsThese results demonstrate that BPA-GA is transferred into the fetus and deconjugated in the fetus because of its vulnerable drug-metabolizing system.
Tissue distribution of DNA adducts and their persistence in blood of mice exposed to benzene.
Authors: G Li, C Wang, W Xin, S Yin
Journal: Environmental Health Perspectives (1996)

Chemicals combine with DNA, resulting in DNA damage, which could initiate carcinogenesis. To study whether benzene or benzene metabolites bind to DNA, DNA adducts in various tissues and their persistence in leukocytes were examined using the 32P-postlabeling assay. LACA mice were dosed ip with benzene at 500 mg/kg bw twice for 5 days. Two additional spots of DNA adducts are formed in bone marrow cells, liver cells, and peripheral blood compared with control mice. The relative adduct labeling values are 10.39, 11.32, and 13.77 adducts x 10(-8) nucleotides in these tissues, respectively. DNA adducts in blood leukocytes were observed at 1, 4, 7, 14, and 21 days after exposure to benzene, but adduct levels decreased as a function of time. Relative adduct labeling of "adduct B" declined linearly but mildly, while "adduct C" displayed a stepwise decrease. The relative adduct labeling values of both these adducts at day 14 were 50% of those at day 1 after the last treatment. Both adducts were still detectable at day 21 after benzene exposure. These studies demonstrate that benzene could induce DNA adducts in bone marrow, liver, and white blood cells of mice dosed with benzene and that measurement of adducts in white blood cells may be useful as a biomarker to predict carcinogenic risk of benzene to workers exposed to benzene.
Diuretic Renography and Urodynamic Pressure Studies in Evaluating Dilated Bilharzial Ureters A Preliminary Report
Authors: HINDURAO N. PAWAR, HUSSEIN M. ABDEL-DAYEM
Journal: Clinical Nuclear Medicine (1984)

A prospective trial was done in 30 ureters in 21 patients using perfusion pressure flow studies (PPFS) and diuretic renography with washout technique (DRWT) in dilated bilharzial ureters in order to diagnose the presence or absence of obstruction and to compare the results. PPFS could not be done in 11 ureters due to technical problems. Three categories of results were obtained: 1) no obstruction could be demonstrated by either PPFS or diuretic renography (11 ureters), 2) obstruction was confirmed by both methods (three ureters), and 3) obstruction was shown by DRWT but could not be proven by PPFS (five ureters). DRWT, which is a noninvasive method, gave the correct diagnosis in the majority of cases and should be the first method used to evaluate dilated bilharzial ureters. In cases where DRWT shows no obstruction, further evaluation is unnecessary, as PPFS did not show obstruction in these cases either. But in cases where obstruction is shown by DRWT, PPFS should be tried to confirm the obstruction before surgery is performed.
EGF Receptor Inhibition Alleviates Hyperuricemic Nephropathy
Authors: Na Liu, Li Wang, Tao Yang, Chongxiang Xiong, Liuqing Xu, Yingfeng Shi, Wenfang Bao, Y. Eugene Chin, Shi-Bin Cheng, Haidong Yan, Andong Qiu, Shougang Zhuang
Journal: Journal of the American Society of Nephrology (2015)

Hyperuricemia is an independent risk factor for CKD and contributes to kidney fibrosis. In this study, we investigated the effect of EGF receptor (EGFR) inhibition on the development of hyperuricemic nephropathy (HN) and the mechanisms involved. In a rat model of HN induced by feeding a mixture of adenine and potassium oxonate, increased EGFR phosphorylation and severe glomerular sclerosis and renal interstitial fibrosis were evident, accompanied by renal dysfunction and increased urine microalbumin excretion. Administration of gefitinib, a highly selective EGFR inhibitor, prevented renal dysfunction, reduced urine microalbumin, and inhibited activation of renal interstitial fibroblasts and expression of extracellular proteins. Gefitinib treatment also inhibited hyperuricemia-induced activation of the TGF-β1 and NF-κB signaling pathways and expression of multiple profibrogenic cytokines/chemokines in the kidney. Furthermore, gefitinib treatment suppressed xanthine oxidase activity, which mediates uric acid production, and preserved expression of organic anion transporters 1 and 3, which promotes uric acid excretion in the kidney of hyperuricemic rats. Thus, blocking EGFR can attenuate development of HN via suppression of TGF-β1 signaling and inflammation and promotion of the molecular processes that reduce uric acid accumulation in the body.
Adverse Outcomes of Underuse of β-Blockers in Elderly Patients
Authors: Herman A. Hein
Journal: JAMA (1997)

<h3>To the Editor.</h3> —I read with interest the Editorial by Drs Felch and Scanlon.1 They speak of the dream for medicine for the new millennium, "that the care of patients will be evidence based," and that this can only be "fully realized when the major players in the health care field find improved ways to work together." They close by saying, "We envision the likelihood that new mechanisms will be found to alert clinicians about the existence of innovation. We hold firm to the right of frontline physicians to make the choice of using it (to follow a recommendation) or to cite their reasons for not using it." In Iowa, we are proud to point to the existence of a program that for the past 24 years has done this very thing—the Iowa Statewide Perinatal Care Program. This program consists of a perinatal review team that includes a maternal-fetal medicine specialist, a neonatologist,
The limits of chimpanzee-human comparisons for understanding human cognition
Authors: Simon M. Reader, Steven M. Hrotic
Journal: Behavioral and Brain Sciences (2012)

Abstract Evolutionary questions require specialized approaches, part of which are comparisons between close relatives. However, to understand the origins of human tool behavior, comparisons with solely chimpanzees are insufficient, lacking the power to identify derived traits. Moreover, tool use is unlikely a unitary phenomenon. Large-scale comparative analyses provide an alternative and suggest that tool use co-evolves with a suite of cognitive traits.
History of eczema herpeticum is associated with the inability to induce human β-defensin (HBD)-2, HBD-3 and cathelicidin in the skin of patients with atopic dermatitis
Authors: T.R. Hata, P. Kotol, M. Boguniewicz, P. Taylor, A. Paik, M. Jackson, M. Nguyen, F. Kabigting, J. Miller, M. Gerber, D. Zaccaro, B. Armstrong, R. Dorschner, D.Y.M. Leung, R.L. Gallo
Journal: British Journal of Dermatology (2010)

Conflicts of interest: None declared. Madam, Patients with atopic dermatitis (AD) with a history of eczema herpeticum (ADEH) represent a subset of individuals with AD who have more severe disease.1 It has previously been shown that the skin of patients with AD has defects in its capacity to increase maximally the antimicrobial peptides (AMPs), cathelicidin, human β‐defensin (HBD)‐2 and HBD‐3 in response to inflammation, in contrast to patients with psoriasis who also have inflammation of the skin, but no difficulty with AMP induction.2, 3 To date, however, previous studies have not examined HBD‐2 and HBD‐3 induction in the ADEH subset of patients.4 We sought to examine if subjects with ADEH exhibit an inhibition in induction of AMPs, compared with subjects without ADEH. A total of 81 subjects were recruited into the study: 26 patients with psoriasis, 21 with AD and nine with ADEH and 25 healthy subjects with no history of skin disease (Table S1, see Supporting information). Two 2‐mm punch biopsies were collected from lesional and nonlesional skin of the patients. Normal controls provided two 2‐mm punch biopsies from the skin of their upper inner arm. Quantification of cathelicidin, interleukin (IL)‐13, HBD‐2 and HBD‐3 in the skin was performed by quantitative reverse transcriptase–polymerase chain reaction (RT‐PCR) (Data S2, see Supporting information), and their expression was calculated as relative to glyceraldehyde 3‐phosphate dehydrogenase (GAPDH) mRNA. All statistical analyses were performed using SAS v.9.1 or higher (SAS Institute, Cary, NC, U.S.A.) (Data S1, see Supporting information).
Hyperuricemia: A Marker for Cell Energy Crisis
Authors: Irving H. Fox, Thomas D. Palella, William N. Kelley
Journal: New England Journal of Medicine (1987)

The underlying cause of hyperuricemia is often obscure. Why are serum urate levels markedly elevated in some acutely ill patients in the intensive care unit?1 What lies behind reports of uric acid nephropathy after heavy exertion?2 What is the association between ethanol ingestion and hyperuricemia?3 Why is gout characteristic of glycogen storage disease?4 The development of hyperuricemia in these apparently unrelated clinical situations, as well as many others, appears to be explained by a single pathogenetic mechanism, the net degradation of ATP.5 6 7 ATP is a ubiquitous, intracellular, high-energy phosphate compound involved in intermediate metabolism. Its synthesis and consumption are dynamic . . .
THE INFLUENCE OF CARBOHYDRATES ON THE CULTIVATION OF SPIROCHETES
Authors: Seinai Akatsu
Journal: The Journal of Experimental Medicine (1917)

Various carbohydrates have been added to the fluid cultures of different strains of spirochetes in order to determine the behavior of the latter toward the carbohydrates. In the present experiment, amygdalin, arabinose, beerwort, dextrin, galactose, glycogen, glucose, inulin, lactose, levulose, maltose, mannite, raffinose, saccharose, and starch were tested with seven strains of Treponema pallidum and one strain each of Treponema calligyrum, Treponema microdentium, Treponema mucosum, and Spirochata refringens. The results may be summarized as follows: 1. In the media containing glycogen and glucose, Treponema microdentium did not grow as vigorously as in other sugar media, and an earlier degeneration set in. One strain of the pallidum and the calligyrum and mucosum showed a poor growth in the glycogen medium. Similarly, there was little growth in the second transfer of these spirochetes in the glucose medium. The growth of the spirochetes in the media containing carbohydrates other than those Just mentioned was generally good, and no difference could be distinguished between these and the control cultures without any carbohydrate. The only phenomenon which might be interpreted as indicating a favorable influence of these media upon growth was the abundant growth of the mucosum, which showed uniform length, regular curves, and active motility somewhat better than in the sugar-free medium. 2. The height of acidity was found in the cultures containing glycogen and glucose in the microdentium, amounting to 0.1 N 4.8 cc. for 10 cc. of the fluid culture. In the other sugar media the acidity varied between 0.1 N 2 cc. and 0.1 N 3.2 cc. for the same amount. In the control cultures, the acidity fluctuated from 0.1 N 0.8 cc. to 0.1 N 2 cc. There was no visible alteration in the appearance of the media after the spirochetes had grown for 3 or 4 weeks. In the case of Treponema microdenlium, a slight opalescence developed in the glycogen and glucose media after several weeks' standing, but there was no precipitation or coagulation of the proteins of the culture media. 3. There was no unusual morphological change in the spirochetes grown in the media containing any of the carbohydrates employed. The only phenomena which should be mentioned are (a) the frequent presence of the terminal appendages (or projections) in the refringens, and in most of the pallidum strains, and (b) the appearance of minute, retractile spherical bodies along the side of the spirochetes in the microdenlium cultivated in the glucose or glycogen media. Judging from the earlier degeneration of the species in the above mentioned media, these peculiar bodies may be interpreted as indicating a phase of plasmoptysis associated with the unfavorable surroundings prior to degeneration. Experimental evidence was not found for considering these spherules as a resistant or spore form of the spirochete.
Development and evaluation of a sublingual tablet based on recombinant Bet v 1 in birch pollen‐allergic patients
Authors: E. Nony, J. Bouley, M. Le Mignon, P. Lemoine, K. Jain, S. Horiot, L. Mascarell, M. Pallardy, R. Vincentelli, P. Leone, A. Roussel, T. Batard, K. Abiteboul, B. Robin, O. de Beaumont, M. Arvidsson, S. Rak, P. Moingeon
Journal: Allergy (2015)

Sublingual immunotherapy (SLIT) applied to type I respiratory allergies is commonly performed with natural allergen extracts. Herein, we developed a sublingual tablet made of pharmaceutical-grade recombinant Bet v 1.0101 (rBet v 1) and investigated its clinical safety and efficacy in birch pollen (BP)-allergic patients.Following expression in Escherichia coli and purification, rBet v 1 was characterized using chromatography, capillary electrophoresis, circular dichroism, mass spectrometry and crystallography. Safety and efficacy of rBet v 1 formulated as a sublingual tablet were assessed in a multicentre, double-blind, placebo-controlled study conducted in 483 patients with BP-induced rhinoconjunctivitis.In-depth characterization confirmed the intact product structure and high purity of GMP-grade rBet v 1. The crystal structure resolved at 1.2 Å documented the natural conformation of the molecule. Native or oxidized forms of rBet v 1 did not induce the production of any proinflammatory cytokine by blood dendritic cells or mononuclear cells. Bet v 1 tablets were well tolerated by patients, consistent with the known safety profile of SLIT. The average adjusted symptom scores were significantly decreased relative to placebo in patients receiving once daily for 5 months rBet v 1 tablets, with a mean difference of 17.0-17.7% relative to the group treated with placebo (P < 0.025), without any influence of the dose in the range (12.5-50 μg) tested.Recombinant Bet v 1 has been produced as a well-characterized pharmaceutical-grade biological drug. Sublingual administration of rBet v 1 tablets is safe and efficacious in patients with BP allergic rhinoconjunctivitis.
1013-118 Impaired coronary microcirculation evidenced by abnormal thrombolysis in myocardial infarction frame counts in patients with transient left ventricular apical ballooning syndrome
Authors: Kevin A Bybee, Abhiram Prasad, Gregory W Barsness, Amir Lerman, Joseph G Murphy, Allan S Jaffe, R.Scott Wright, Charanjit S Rihal
Journal: Journal of the American College of Cardiology (2004)