tbuckley/cabot-search huggingface dataset:
Antagonistic Roles of CD4+ and CD8+ T-Cells in 7,12-Dimethylbenz(<i>a</i>)anthracene Cutaneous Carcinogenesis
Authors: Nabiha Yusuf, Tahseen H. Nasti, Santosh K. Katiyar, Michael K. Jacobs, Megan D. Seibert, Alexis C. Ginsburg, Laura Timares, Hui Xu, Craig A. Elmets
Journal: Cancer Research (2008)

Abstract The role that cell-mediated immune responses play during cutaneous carcinogenesis has received little attention. In this study, we evaluated the contribution of CD4+ and CD8+ T cells in C3H/HeN mice that were subjected to a two-stage 7,12-dimethylbenz(a)anthracene (DMBA) initiation, 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion skin carcinogenesis protocol. In CD8 knockout (CD8−/−) mice, allergic contact hypersensitivity to DMBA was reduced compared with wild-type (WT) C3H/HeN mice. On the other hand, CD4 knockout (CD4−/−) mice developed an exaggerated contact hypersensitivity response. CD4+ T cells from DMBA contact–sensitized mice preferentially produced interleukin 4 (IL-4), IL-10, and IL-17; CD8+ T cells, on the other hand, secreted IFN-γ. When CD4−/−, CD8−/−, and WT mice were subjected to a standard two-stage DMBA/TPA cutaneous carcinogenesis protocol, the percentage of mice with tumors was much greater (P &amp;lt; 0.001) in CD8−/− mice than in WT mice. In contrast, the percentage of tumors was significantly less (P &amp;lt; 0.001) in CD4−/− mice than in WT mice. Similar results were obtained when the data were evaluated as the number of tumors per mouse. These findings indicate that (a) CD8+ T cells are the predominant effector cells in allergic contact hypersensitivity to DMBA and that CD4+ T cells have an inhibitory role and (b) the development of CD8+ T cells plays a protective role in skin tumor development whereas CD4+ T cells have the opposite effect. Manipulation of T-cell subpopulations that are induced by carcinogenic chemicals, like DMBA, could be a means of preventing skin cancers caused by these agents. [Cancer Res 2008;68(10):3924–30]
Howell-Jolly Bodies and Splenectomy
Authors: David Kohn
Journal: JAMA (1983)

<h3>To the Editor.—</h3> Concerning the question and the reply to determine residual spleen tissue after traumatic splenectomy (1982;247:2037), the presence of Howell-Jolly bodies in peripheral blood erythrocytes strongly supports the absence of spleen. In the absence of Howell-Jolly bodies, there must be some splenic tissue.
Intervertebral disc regeneration after implantation of a cell-free bioresorbable implant in a rabbit disc degeneration model
Authors: Michaela Endres, Alexander Abbushi, Ulrich W. Thomale, Mario Cabraja, Stefan N. Kroppenstedt, Lars Morawietz, Pablo A. Casalis, Maria L. Zenclussen, Arne-Jörn Lemke, Peter Horn, Christian Kaps, Christian Woiciechowsky
Journal: Biomaterials (2010)
First Surgical Success in Hirschsprung's Disease
Authors: Max Landsberger
Journal: JAMA (1965)

To the Editor:—  It is no rare occurrence that conceptions in medicine change from one position to the opposite. A striking illustration is the history of congenital megacolon since Hirschsprung's 1 description in 1887. For decades medical literature focused all the attention on the dilated and hypertrophied colon, but resection did not achieve cure and frequently was followed by recurrence. The etiology remained obscure, and numerous theories were offered, which Swenson and his collaborators 2 reviewed in 1949. Absence of the myenteric plexus in the distal part of the colon was observed by several investigators since 1920, which finally led to Swenson's recognition that the aganglionic segment of the innocent-looking area, essentially the sigmoid and rectum, was the cause of functional obstruction with secondary proximal dilation and hypertrophy. New diagnostic procedures, especially radiological demonstration of a narrow lumen distal to the ballooning bowel 3 and rectal biopsy 4 with histological
The role of cytokines in the generation of inflammation and tissue damage in experimental gram-positive meningitis.
Authors: K Saukkonen, S Sande, C Cioffe, S Wolpe, B Sherry, A Cerami, E Tuomanen
Journal: The Journal of Experimental Medicine (1990)

Cytokines mediate many host responses to bacterial infections. We determined the inflammatory activities of five cytokines in the central nervous system: TNF-alpha, IL-1 alpha, IL-1 beta, macrophage inflammatory protein 1 (MIP-1), and macrophage inflammatory protein 2 (MIP-2). Using a rabbit model of meningeal inflammation, each cytokine (except IL-1 beta) induced enhanced blood brain barrier permeability, leukocytosis in cerebrospinal fluid, and brain edema. Homologous antibodies to each mediator inhibited leukocytosis and brain edema, and moderately decreased blood brain barrier permeability. In rabbits treated with anti-CD-18 antibody to render neutrophils dysfunctional for adhesion, each cytokine studied lost the ability to cause leukocytosis and brain edema. After intracisternal challenge with pneumococci, antibodies to TNF or IL-1 prevented inflammation, while anti-MIP-1 or anti-MIP-2 caused only a 2-h delay in the onset of inflammation. We suggest these cytokines have multiple inflammatory activities in the central nervous system and contribute to tissue damage during pneumococcal meningitis.
Herbert (“Bert”) Spencer Kellett
Authors: Michael Kellett
Journal: BMJ (2006)

​FormerFormer consultant pathologist Bradford Royal Infirmary (b 1912; q Cambridge and Middlesex Hospital, London, 1938; MD, FRCPath), d 26 January 2006.



Figure 1



Herbert Spencer Kellett (“Bert”) was a well-respected pathologist, particularly in the histopathology of lymphomas and bone tumours. After his first year at Emmanuel College, Cambridge, he changed from chemistry to medical subjects, obtaining a first in biochemistry part 2 on the Krebs cycle. He was appointed as the second consultant pathologist to the Bradford Royal Infirmary in 1948, starting as a general pathologist dealing with all aspects of pathology, and retired in 1977. In retirement he continued to work part time at the Leeds Cancer Centre, where he set up a regional register of lymphomas at Cookridge. Predeceased by his wife, Muriel, in 1995, he leaves two sons and four grandchildren.
Glad to be here
Authors: Adrian Manning
Journal: BMJ (2009)

In December 2007 my 56 year old younger brother, living and working in a major city in the United States, underwent his routine yearly company medical examination. He phoned me afterwards to ask what the “PSA” was, because his was high. I, an NHS gastroenterologist, gave him our party line: the prostate specific antigen (PSA) test can indicate prostate cancer but has too many flaws to be useful for screening. He had a transrectal biopsy, which he described to me vividly, and it showed cancer. His urologist proposed robot assisted laparoscopic radical prostatectomy. The urologist said that this was the only operation considered these days; he did no other. It was, he said, best for reducing blood loss, for speed of recovery, and for nerve sparing and hence potency; any right thinking second opinion giver would say the same.

I did what many patients, relatives, and doctors do: I consulted the internet. Among many helpful (and unhelpful) things I learnt was that a major risk factor for prostate cancer is a positive family history. We had no …
Elevated Creatinine Levels and Quality of Care in Heart Failure
Authors: Linda Fried
Journal: Annals of Internal Medicine (2007)

Letters6 November 2007Elevated Creatinine Levels and Quality of Care in Heart FailureLinda Fried, MD, MPHLinda Fried, MD, MPHFrom Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA 15240.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-147-9-200711060-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read the recent article by Baker and colleagues (1) with interest. I was concerned that end-stage renal disease and chronic renal insufficiency were listed as valid exclusions for why individuals are not receiving an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) in heart failure. This is not consistent with current guidelines, and the Agency for Healthcare Research and Quality recommendations state that an elevated creatinine level is not an exclusion (2). Subgroup analyses of studies do not suggest a lower benefit of ACE inhibitors or ARBs (3) and as individuals with an elevated creatinine level ...References1. Baker DW, Persell SD, Thompson JA, Soman NS, Burgner KM, Liss D, et al. Automated review of electronic health records to assess quality of care for outpatients with heart failure. Ann Intern Med. 2007;146:270-7. [PMID: 17310051] LinkGoogle Scholar2. Agency for Healthcare Research and Quality. Clinical practice guidelines archive. Accessed at www.ahrq.org/clinic/cpgarchv.htm on 28 August 2007. Google Scholar3. Frances CD, Noguchi H, Massie BM, Browner WS, McClellan M. Are we inhibited? Renal insufficiency should not preclude the use of ACE inhibitors for patients with myocardial infarction and depressed left ventricular function. Arch Intern Med. 2000;160:2645-50. [PMID: 10999979] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA 15240.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAutomated Review of Electronic Health Records to Assess Quality of Care for Outpatients with Heart Failure David W. Baker , Stephen D. Persell , Jason A. Thompson , Neilesh S. Soman , Karen M. Burgner , David Liss , and Karen S. Kmetik Elevated Creatinine Levels and Quality of Care in Heart Failure David W. Baker , Stephen D. Persell , and Karen S. Kmetik Metrics 6 November 2007Volume 147, Issue 9Page: 672KeywordsACE inhibitorsConflicts of interestCreatinineHealth care qualityHealth services researchHeart failureRenal diseasesRenal failureResearch quality assessment ePublished: 6 November 2007 Issue Published: 6 November 2007 CopyrightCopyright © 2007 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
N-hydroxylation of carcinogenic and mutagenic aromatic amines.
Authors: R Kato, T Kamataki, Y Yamazoe
Journal: Environmental Health Perspectives (1983)

N-Hydroxylation and mutagenic activation of heterocyclic aromatic amines from protein pyrolysis products were studied in rat liver microsomes and nuclei, rat hepatocytes and various species of purified cytochrome P-450. These mutagenic amines include Trp-P-2 (3-amino-1-methyl-5H-pyrido[4,3-b]indole), Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole), Glu-P-1 (2-amino-6-methyldipyrido-[1,2-a:3',2'-d]imidazole), Glu-P-2 (2-amino-dipyrido[1,2-a:3',2'-d]imidazole) and IQ (2-amino-3-methyl-3H-imidazo-[4,5-f]quinoline). The number of revertants of Salmonella typhimurium TA 98 was always correlated to the amount of each of the N-hydroxylated metabolites in various experimental conditions. The N-hydroxylated amines covalently bound to DNA directly or after being acylated with amino acids by amino-acyl-tRNA synthetase. Various species of cytochrome P-450 preparations showed markedly different activity in N-hydroxylation and mutagenic activation of Trp-P-2, Glu-P-1 and IQ. A high spin form of cytochrome P-450, isolated from the liver of PCB-treated rats, showed very high activity in N-hydroxylation of Trp-P-2, Glu-P-1 and 2-aminofluorene, although its activity was very low in benzo(a)pyrene hydroxylation. The present results indicate that different species of cytochrome P-450 are involved in the N-hydroxylation and mutagenic activation of aromatic amines.
Variations in population health status: results from a United Kingdom national questionnaire survey
Authors: P. Kind, P. Dolan, C. Gudex, A. Williams
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To measure the health of a representative sample of the population of the United Kingdom by using the EuroQoL EQ-5D questionnaire. <b>Design</b>: Stratified random sample representative of the general population aged 18 and over and living in the community. <b>Setting</b>: United Kingdom. <b>Subjects:</b> 3395 people resident in the United Kingdom. <b>Main outcome measures:</b> Average values for mobility, self care, usual activities, pain or discomfort, and anxiety or depression. <b>Results:</b> One in three respondents reported problems with pain or discomfort. There were differences in the perception of health according to the respondent9s age, social class, education, housing tenure, economic position, and smoking behaviour. <b>Conclusions:</b> The EQ-5D questionnaire is a practical way of measuring the health of a population and of detecting differences in subgroups of the population. <h3>Key messages</h3> Measurement of health outcome requires the observation of states of health Patients9 involvement in recording and assessing their own state of health is a major element in the process of evaluating the impact of health care The EuroQoL EQ-5D questionnaire highlights variations in states of health which are consistent with previously published results High degrees of pain are reported in the general population. A category for pain is absent and thus undetected in the survey of disability by the Office of Population Censuses and Surveys
Chronic ulcerative stomatitis
Authors: B. WÖRLE, A. WOLLENBERG, M. SCHALLER, K.‐H. KUNZELMANN, G. PLEWIG, M. MEURER
Journal: British Journal of Dermatology (1997)

Chronic ulcerative stomatitis (CUS) has recently been described as a new disease entity characterized by chronic ulceration of oral mucosa which responds to treatment with hydroxychloroquine. It has a particular type of stratified epithelium‐specific, antinuclear autoantibody as an immunological marker. Twelve cases have been reported in the literature. We present a 40‐year‐old woman with an 11‐year history of chronic oral ulcerations. Other dermatological diseases, including oral lichen planus, pemphigus vulgaris and cicatricial pemphigoid, as well as bullous lupus erythematosus, were excluded. The clinical diagnosis of CUS was confirmed on the ground of the immunological and ultrastructural findings. The lesions initially responded to high doses of systemic corticosteroids but relapsed promptly after dose reduction. Dapsone was ineffective. Hydroxychloroquine, given at a dosage of 200–400 mg/day, led to a complete and longlasting remission.
In Vitro and In Vivo Efficacy of SYL040012, a Novel siRNA Compound for Treatment of Glaucoma
Authors: Tamara Martínez, Maria Victoria González, Ingo Roehl, Natalia Wright, Covadonga Pañeda, Ana Isabel Jiménez
Journal: Molecular Therapy (2013)

Glaucoma is a progressive ocular syndrome characterized by degeneration of the optic nerve and irreversible visual field loss. Elevated intraocular pressure (IOP) is the main risk factor for glaucoma. Increased IOP is the result of an imbalance between synthesis and outflow of aqueous humor (AH). Blocking β2 adrenergic receptor (ADRB2) has shown to reduce IOP by decreasing production of AH at the ciliary body (CB). SYL040012 is a siRNA designed to specifically silence ADRB2 currently under development for glaucoma treatment. Here, we show that SYL040012 specifically reduces ADRB2 expression in cell cultures and eye tissues. The compound enters the eye shortly after administration in eye drops and is rapidly distributed among structures of the anterior segment of the eye. In addition, SYL040012 is actively taken up by cells of the CB but not by cells of systemic organs such as the lungs, where inhibition of ADRB2 could cause undesirable side effects. Moreover, SYL040012 reduces IOP in normotensive and hypertensive animal models and the effect appears to be long lasting and extremely well tolerated both locally and systemically. Glaucoma is a progressive ocular syndrome characterized by degeneration of the optic nerve and irreversible visual field loss. Elevated intraocular pressure (IOP) is the main risk factor for glaucoma. Increased IOP is the result of an imbalance between synthesis and outflow of aqueous humor (AH). Blocking β2 adrenergic receptor (ADRB2) has shown to reduce IOP by decreasing production of AH at the ciliary body (CB). SYL040012 is a siRNA designed to specifically silence ADRB2 currently under development for glaucoma treatment. Here, we show that SYL040012 specifically reduces ADRB2 expression in cell cultures and eye tissues. The compound enters the eye shortly after administration in eye drops and is rapidly distributed among structures of the anterior segment of the eye. In addition, SYL040012 is actively taken up by cells of the CB but not by cells of systemic organs such as the lungs, where inhibition of ADRB2 could cause undesirable side effects. Moreover, SYL040012 reduces IOP in normotensive and hypertensive animal models and the effect appears to be long lasting and extremely well tolerated both locally and systemically.
Elevated levels of cytokeratin 19 in the bronchoalveolar lavage fluid of patients with chronic airway inflammatory diseases--a specific marker for bronchial epithelial injury.
Authors: H Nakamura, S Abe, Y Shibata, H Yuki, H Suzuki, H Saito, M Sata, S Kato, H Tomoike
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Cytokeratin 19 (CK19) is a specific cytoskeletal structure of simple epithelia, including bronchial epithelial cells (BEC). Since CK19 is released from injured bronchial epithelium, we investigated the levels of CK19 fragments in the bronchoalveolar lavage fluid (BALF) of eight patients with chronic airway inflammatory diseases (CAID) using an enzyme-linked immunosorbent assay (ELISA). Included in our test group were four cases of chronic bronchitis, three cases of bronchiectasis, and one case of diffuse panbronchiolitis. There were also 15 control subjects (five asymptomatic smokers and 10 nonsmokers). BALF from the nonsmokers as well as from the asymptomatic smokers contained few CK19 fragments (0.2 +/- 0.2 and 1.9 +/- 0.8 pg/ml, respectively). In contrast, significantly high levels of CK19 were present in the BALF of patients with CAID (21.7 +/- 5.7 pg/ml; p < 0.01 versus nonsmoking controls). In addition, CK19 fragment concentrations in BALF correlated significantly with the number of neutrophils (r = 0.722, p < 0.01) but not with the numbers of macrophages or lymphocytes in BALF. BALF from patients with CAID contained high levels of neutrophil elastase (NE) activity, suggesting that NE might be an important stimulus for the release of CK19 from BEC. To prove this, we incubated BET-1A cells, a human immortalized bronchial epithelial cell line, both in the absence and the presence of inflammatory mediators (including NE, tumor necrosis factor-alpha [TNF-alpha], and hydrogen peroxide). We then measured the concentration of CK19 fragments in the culture supernatants with ELISA. BET-1A cells released CK19 fragments into their culture supernatants after treatment with NE but not after treatment with TNF or hydrogen peroxide. Further, we demonstrated that CK19 cleaved by NE could not be detected by ELISA. Our results suggest that CK19 measurement in BALF is useful for assessing the presence of bronchial epithelial injuries.
Clinical Use of a Protein-Sparing Modified Fast
Authors: Bruce R. Bistrian
Journal: JAMA (1978)

OBESITY is notoriously resistant to treatment. Short-term weight reduction of greater than 18 kg occurs in fewer than 5% of outpatients.<sup>1</sup>Possible explanations for noncompliance and ineffectiveness of conventional diet therapy include hunger and the disappointingly slow rate of weight loss. Total fasting reduces hunger and induces rapid weight loss,<sup>2</sup>but half the weight loss in the first month and one fourth to one third thereafter is from muscle tissue,<sup>3</sup>and hepatic, renal, and endocrine function is affected. For these reasons fasting regimens are generally recommended only for inpatients. Long-term follow-up of persons who previously fasted has demonstrated a high rate of recidivism<sup>5</sup>due to obligate regain of lean tissue or the lack of a weight-maintenance program or both. When a fast is supplemented by small amounts of protein in the form of egg albumin,<sup>6</sup>casein,<sup>7</sup>casein with glucose,<sup>8</sup>or amino acids with
Concurrent pityriasis rotunda and acquired ichthyosis with IgG myeloma
Authors: JUNJI IKADA, MORIO OKI
Journal: British Journal of Dermatology (1974)

Journal Article Concurrent pityriasis rotunda and acquired ichthyosis with IgG myeloma Get access JUNJI IKADA, JUNJI IKADA Department of Dermatology, Kyoto Prefectural University of Medicine, Kawara‐machi, Hirokoji, Kamikyo‐ku, Kyoto, Japan Search for other works by this author on: Oxford Academic Google Scholar MORIO OKI MORIO OKI Department of Dermatology, Kyoto Prefectural University of Medicine, Kawara‐machi, Hirokoji, Kamikyo‐ku, Kyoto, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 91, Issue 5, 1 November 1974, Pages 585–586, https://doi.org/10.1111/j.1365-2133.1974.tb12949.x Published: 01 November 1974 Article history Accepted: 20 February 1974 Published: 01 November 1974
Correlates of Severe or Life-Threatening Toxic Effects From Trimetrexate
Authors: J. L. Grem, S. S. Ellenberg, S. A. King, D. D. Shoemaker
Journal: JNCI Journal of the National Cancer Institute (1988)

Trimetrexate, an investigational antifol, has been associated with marked variability in drug tolerance among patients. The agent is extensively protein bound, and hepatic biotransformation plays a major role in its elimination. In early phase II testing, nine of 15 patients who experienced life-threatening or fatal toxic effects from trimetrexate had albumin levels less than or equal to 3.5 g/dL prior to treatment. This prompted a review of the data base on 272 patients entered in phase I clinical trails. The incidence of severe or life-threatening anemia, leukopenia, neutropenia, thrombocytopenia, mucositis, and hepatic toxic effects during the first course of trimetrexate was analyzed according to dose, schedule, prior treatment, and baseline protein and albumin levels. The schedules using doses given by short infusions of 30-60 minutes daily for 5 days or weekly for 3 weeks were generally associated with higher incidence of toxic effects than the schedules using doses given every other week by short infusions or those using continuous infusion. The occurrence of leukopenia and mucositis was dose related. Patients with baseline albumin levels less than or equal to 3.5 g/dL had higher incidence of all types of severe or life-threatening toxic effects than those with albumin levels greater than or equal to 3.6 g/dL, and the differences were significant for the development of anemia, thrombocytopenia, and mucositis. Similar correlations were noted for pretreatment protein levels less than or equal to 6.0 g/dL. The small cohort of patients with leukemia experienced substantial toxic effects and tended to have low protein and albumin levels. Performance status and prior therapy did not emerge as strong predictors of severe toxic effects in the univariate analysis. Multivariate analysis confirmed that the type of cancer (leukemia vs. solid tumor), dose, schedule, and baseline albumin level were significant and independent predictors of severe and life-threatening toxic effects in the phase I patient population. Multivariate analysis including only patients with solid tumors indicated that albumin level, dose, and schedule remained significant predictors of toxic effects. Since normal liver function as reflected by bilirubin and transaminase values were a requirement for eligibility, the results suggest that albumin and protein levels may provide a more sensitive index of hepatic function. Patients with hypoalbuminemia and hypoproteinemia are at increased risk of experiencing severe or life-threatening toxic effects from trimetrexate and should be treated cautiously.