tbuckley/cabot-search huggingface dataset:
Ileal and colonic fatty acid profiles in patients with active Crohn's disease.
Authors: S Buhner, E Nagel, J Korber, H Vogelsang, T Linn, R Pichlmayr
Journal: Gut (1994)

In patients with active Crohn's disease and in a control group the fatty acid profiles in the whole lipid fraction of ileal and colonic mucosal biopsy specimens were determined by capillary gas chromatography. The biopsy specimens in Crohn's disease patients were taken from the inflamed terminal ileum as well as from the inflamed and macroscopically normal colon. Compared with controls the fatty acid distribution in the inflamed ileal mucosa was significantly characterised by (a) a decrease of 18:2 n6 and 18:3 n3 accompanied by a substantial increase of the highly polyunsaturated fatty acids 20:4 n6, 22:4 n6, and 22:6 n3 and (b) a higher unsaturation index of total fatty acids compared with controls. These changes were similar in the inflamed colon. Additionally, both the inflamed and the macroscopically normal colonic mucosa showed an increase of saturated (18:0) and a decrease of monounsaturated fatty acids (18:1 n9). Fatty acid profiles of ileum and colon showed side variations in controls, but not in the Crohn's disease group. These data suggest that in Crohn's disease changes in the distribution of polyunsaturated fatty acids seem to be the general feature of inflamed mucosa in small and large intestine. Results further suggest that colonic fatty acid metabolism in Crohn's disease is altered by degrees, showing changes in saturated and monounsaturated fatty acids as an additional, primary event.
B3-02: Randomized, double-blind, multicenter, parallel-group, Phase II study of gefitinib (IRESSA) plus best supportive care (BSC) versus placebo plus BSC in chemotherapy-naïve patients with advanced non-small-cell lung cancer and poor performance status (INSTEP)
Authors: Glenwood Goss, David Ferry, Scott Laurie, Rafal Wierzbicki, Joyce Thompson, B Biesma, Emma Duffield, Serban Ghiorghiu, Marc Zarenda, Alison Armour
Journal: Journal of Thoracic Oncology (2007)
Differentiation and activation of regulatory T lymphocytes in a TNF transgenic model of arthritis, and the impact of passive or active anti-TNF therapies
Authors: J. Biton, L. Semerano, L. Delavallee, D. Lemeiter, M. Laborie, G. Grouard-Vogel, M.-C. Boissier, N. Bessis
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Tumour necrosis factor (TNF) is a critical cytokine in rheumatoid arthritis. The authors recently demonstrated the efficacy of active immunotherapy against TNF (TNF-K) in a human TNF transgenic (TTg) mouse model of arthritis. Studies with anti-TNF treatments in autoimmune diseases suggest that TNF and TNF antagonists might act through the involvement of a T cells subset, namely CD4<sup>+</sup> CD25<sup>+</sup> FoxP3<sup>+</sup> regulatory T cells (Treg). In the present study, the authors aimed to better characterise the impact on the Treg population of (1) a TNF driven disease, specifically arthritis in TTg mice and (2) active or passive anti-TNF immunotherapy in this same model. <h3>Methods</h3> First, untreated TTg mice were euthanised sequentially at the age of 7 weeks, 12 weeks, 17 weeks and 24 weeks. Subsequently, three groups of mice were used: TTg mice given three doses of TNF-K at 15, 16 and 19 weeks of age, TTg mice treated with infliximab and untreated TTg mice. Then in each group, mice were euthanised at 31 weeks. After each euthanasia, the frequency of Treg and the percentage of Treg cells expressing CTLA-4, TNFR2 and CD62L from the spleen and lymph nodes (LN) were determined. Finally, the immunosuppressive activity of the Treg cells was studied. <h3>Results</h3> hTNF overexpression induced an initial decline in Treg. Then, once chronic inflammation was established, the frequency of Treg cells increased with time. The authors also observed a progressive and dramatic increase in TNFR2 expression (65.8–88.6% at weeks 7 and 24, respectively, p&lt;0,0001) and MFI on Treg from LN during the course of arthritis. Compared to untreated mice, hTNF blockade with either infliximab or TNF-K resulted in an increased Treg frequency. The study also showed that hTNF blockade induces an upregulation of CTLA-4 expression by Treg cells in LN, accompanied by an increased Treg suppressive activity on CD4<sup>+</sup> CD25<sup>−</sup> effector T cell proliferation. Finally, in LN of infliximab and TNF-K treated TTg mice, the authors observed an expansion of induced Treg cells defined by the CD4<sup>+</sup> CD25<sup>+</sup> FoxP3<sup>+</sup> CD62L<sup>−</sup> phenotype. <h3>Conclusion</h3> In this study, in a strictly hTNF dependent inflammation model, the authors show for the first time that TNF can have different effects on Treg, depending on the duration of exposure and on disease phase. The work also shows that TNF blockade either by TNF-K or infliximab could depend not only on TNF neutralisation but also on Treg upregulation.
Cerebral Thrombosis Complicating Abortus Fever
Authors: C. W. Lawson, C. A. Leeson
Journal: BMJ (1954)

MEDICAL MEMORANDA MEDICATLSJORNAL 1 gr.(65 mg.) was absorbed, when allowance is made for dilution of the drug throughout much of the tissues of the body considerably less than the detectable amount must have remained in the relatively small specimens analysed.This is particularly so when it is remembered that some must have been excreted and lost before death occurred.Moreover, only part of the specimens analysed was utilized for the cantharidin test, as these had to be divided into several portions in order to test for other irritants.Grateful acknowledgment is made to Dr. R. T. Gaunt for access to the clinical details of this case.
Roman Stefan Kocen
Authors: J. Scadding
Journal: BMJ (2013)

Aged 11, Roman Stefan Kocen escaped from the Warsaw ghetto in 1943 and reached England in 1946, unable to speak English. At the age of 18, he won a state scholarship to study medicine at Leeds University, qualifying with honours in 1956. After junior posts in Leeds, national service in Malaya, where he was officer in charge …
Influence of topically applied adrenergic agents on cochlear blood flow.
Authors: K A Ohlsén, D L Baldwin, A L Nuttall, J M Miller
Journal: Circulation Research (1991)

This study was designed to assess the role of adrenergic receptors in the control of cochlear blood flow. Laser Doppler flowmetry was used to determine the effects of adrenergic drugs topically applied to the round window membrane of the cochlea. The relative influence of the various receptor types (alpha 1, alpha 2, beta 1, and beta 2) was examined by a selection of agonists and antagonists. The agonists norepinephrine and epinephrine, which have mixed alpha- and beta-receptor effects, and phenylephrine, a strong alpha 1-agonist, all induced a dose-dependent reduction in cochlear blood flow. The agonists isoproterenol (beta-active), salbutamol (alpha 2-active) had no effect on cochlear blood flow. Of the antagonists, when tested alone, only the selective alpha 1-antagonist prazosin had a direct effect on cochlear blood flow, demonstrating an increase in cochlear blood flow. The selective alpha 2-antagonist idazoxan, the beta-antagonist propranolol, and the unselective alpha-antagonist phentolamine had no effect on cochlear blood flow. Interaction studies of agonists and antagonists were performed to specifically define the receptor subclasses responsible for the cochlear blood flow increases with norepinephrine and epinephrine. The results are consistent with the presence of an alpha 1-adrenergic sympathetic control of cochlear blood flow.
Tumor necrosis factor-alpha and interferon-gamma suppress the activation of human type I collagen gene expression by transforming growth factor-beta 1. Evidence for two distinct mechanisms of inhibition at the transcriptional and posttranscriptional levels.
Authors: V M Kähäri, Y Q Chen, M W Su, F Ramirez, J Uitto
Journal: Journal of Clinical Investigation (1990)

Regulation of human type I procollagen gene expression was studied in cultured fibroblasts both at the transcriptional and posttranscriptional level. Transcriptional regulation was examined in cultures transfected with a human pro alpha 2(I) collagen promoter/reporter gene (chloramphenicol acetyltransferase) construct, while posttranscriptional regulation was assessed by parallel determinations of type I procollagen mRNA steady-state levels. Transforming growth factor-beta 1 (TGF-beta 1) elicited a marked, approximately 5-23-fold, enhancement of pro alpha 2(I) collagen promoter activity, which was accompanied by an elevation of type I procollagen mRNA levels. This enhancement of gene expression was suppressed by tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), as determined at mRNA steady-state level, but two distinct mechanisms were involved. TNF-alpha suppressed the pro alpha 2(I) collagen promoter activity, whereas IFN-gamma had only a minimal effect at transcriptional level. The effects of TNF-alpha and IFN-gamma were synergistic, suggesting that combination of these two factors may potentially provide pharmacologic means to counteract tissue deposition of collagen in diseases involving TGF-beta.
Effects of omalizumab on markers of inflammation in patients with allergic asthma
Authors: S. Holgate, N. Smith, M. Massanari, P. Jimenez
Journal: Allergy (2009)

Asthma is a chronic inflammatory disease of the airways in which immunoglobulin E (IgE) plays a key role by activating a variety of inflammatory cells through interactions with FcepsilonRI and FcepsilonRII receptors. The role of IgE in allergic inflammation provided the rationale for developing omalizumab, a humanized monoclonal anti-IgE antibody, for patients with moderate-to-severe or severe allergic asthma. The reductions in circulating levels of IgE resulting from omalizumab treatment leads to reductions in FcepsilonRI expression on mast cells, basophils and dendritic cells. This combined effect results in attenuation of several markers of inflammation, including peripheral and bronchial tissue eosinophilia and levels of granulocyte macrophage colony stimulating factor, interleukin (IL)-2, IL-4, IL-5 and IL-13. By blocking IgE binding to its receptors and diminishing dendritic cell FcepsilonRI receptor expression, omalizumab may also reduce allergen presentation to T cells and the production of Th2 cytokines. The anti-inflammatory effects of omalizumab may, therefore, explain the reductions in asthma exacerbations and symptoms seen in clinical trials in patients with moderate-to-severe or severe, persistent, inadequately controlled allergic asthma.
Opening the Window to Cancer: Potential Mechanism behind Increased Susceptibility in Rats Exposed Prenatally to BPA
Authors: Julia R. Barrett
Journal: Environmental Health Perspectives (2010)

Genotoxicity of Chemicals in Indoor Swimming PoolsDisinfection by-products (DBPs) form in swimming pool water from reactions between disinfectants such as chlorine and organic matter such as sweat, skin cells, and urine.A new study described in a set of three articles provides the first comprehensive characterization of DBPs in an indoor pool environment and offers initial evidence of cellular-level effects of these chemicals in swimmers in an indoor chlorinated pool [
Reducible Poly(oligo-D-arginine) for Enhanced Gene Expression in Mouse Lung by Intratracheal Injection
Authors: Young-Wook Won, Hyun Ah Kim, Minhyung Lee, Yong-Hee Kim
Journal: Molecular Therapy (2009)

Nonarginine (D-R9) has been reported to be one of the most efficacious protein transduction domains (PTDs) for the intracellular cargo delivery such as DNA, RNA, proteins, and particles. Although oligoarginines are capable of forming polyplex with DNA by electrostatic interaction, the length of oligoarginine can affect the toxicity and gene expression. The reducible poly(oligo-D-arginine) (rPOA) composed of the Cys-(D-R9)-Cys repeating unit forming disulfide bonds between terminal cysteinyl-thiol groups of short peptides was hypothesized to show efficient gene transfection without toxicity. The reducible high molecular weight poly(oligo-D-arginine) may fragment into the Cys-(D-R9)-Cys in cellular environments such as cytosol, cell surface, endosomes, and lysosomes, and enhance DNA transfection efficiency. In the present study, in vitro stability, cytotoxicity, and transfection efficiency of DNA/poly(oligo-D-arginine) polyplex were evaluated. In addition, in vivo delivery of DNA into the lung was performed by intratracheal injection of DNA/poly(oligo-D-arginine) polyplex. The in vivo study with rPOA showed higher level of gene expression than PEI, sustaining for 1 week without toxicity. Reducible high molecular weight poly(oligo-D-arginine) based on R9 PTD is a very promising nonviral gene carrier for lung diseases by efficiently condensing, stabilizing, and transfecting DNA. Nonarginine (D-R9) has been reported to be one of the most efficacious protein transduction domains (PTDs) for the intracellular cargo delivery such as DNA, RNA, proteins, and particles. Although oligoarginines are capable of forming polyplex with DNA by electrostatic interaction, the length of oligoarginine can affect the toxicity and gene expression. The reducible poly(oligo-D-arginine) (rPOA) composed of the Cys-(D-R9)-Cys repeating unit forming disulfide bonds between terminal cysteinyl-thiol groups of short peptides was hypothesized to show efficient gene transfection without toxicity. The reducible high molecular weight poly(oligo-D-arginine) may fragment into the Cys-(D-R9)-Cys in cellular environments such as cytosol, cell surface, endosomes, and lysosomes, and enhance DNA transfection efficiency. In the present study, in vitro stability, cytotoxicity, and transfection efficiency of DNA/poly(oligo-D-arginine) polyplex were evaluated. In addition, in vivo delivery of DNA into the lung was performed by intratracheal injection of DNA/poly(oligo-D-arginine) polyplex. The in vivo study with rPOA showed higher level of gene expression than PEI, sustaining for 1 week without toxicity. Reducible high molecular weight poly(oligo-D-arginine) based on R9 PTD is a very promising nonviral gene carrier for lung diseases by efficiently condensing, stabilizing, and transfecting DNA.
Using Low-frequency Oscillation to Detect Bronchodilator Responsiveness in Infants
Authors: MARK J. HAYDEN, FERENC PETAK, ZOLTAN HANTOS, GRAHAM HALL, PETER D. SLY
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The potential of the low-frequency forced oscillation technique (FOT) to measure the response to inhaled salbutamol was studied in 13 infants with a history of recurrent wheeze and nine healthy infants. The input impedance of the respiratory system (Zrs) between 0.5 and 20 Hz was measured at a transrespiratory pressure of 20 cm H2O during a brief Hering-Breuer reflex-induced pause in breathing. Parameters representing the airway resistance (Raw) and inertance (Iaw), and a constant-phase tissue damping (G) and elastance (H) were estimated from the Zrs spectra. Lung function was measured before and after the administration of 500 μ g of salbutamol via a small-volume metal spacer. Six of these infants also received a placebo aerosol. A fall in Raw (13% for the entire group) occurred following treatment with salbutamol (p < 0.008) but not placebo. There was no significant difference in the response to salbutamol between the normal infants (7.65% ± 5.49%) and those with recurrent wheeze (17.58% ± 8.67%). On grouped data, the fall in G just failed to reach statistical significance (p = 0.05) after correcting the significance level for multiple tests. No significant change occurred in Iaw or H. We conclude that the low-frequency FOT is a suitable methodology for studying bronchodilator responsiveness in infants.
Reliability of Histologic Scoring for Lupus Nephritis: A Community-based Evaluation
Authors: Richard M. Wernick
Journal: Annals of Internal Medicine (1993)

To determine the reliability of the National Institutes of Health (NIH)-modified semiquantitative histologic scoring system for lupus nephritis.Cross-sectional study, repeated after 8 to 9 months.Four community hospitals and one university medical center.Five pathologists, all experienced in reading renal biopsy specimens, assessed 25 specimens that had been obtained from patients with a clinical diagnosis of systemic lupus erythematosus and showed diffuse proliferative glomerulonephritis.Biopsy specimens were scored independently and blindly by pathologists for components of nephritis chronicity and activity. Reliability was measured by percentage agreement, intraclass correlation coefficient or kappa statistic, and individual reader effect on the group arithmetic mean.As scored by the readers, the mean chronicity index score varied from 2.3 to 4.8 on a 12-point scale (P = 0.001) and the mean activity index score varied from 5.8 to 11.4 on a 24-point scale (P = 0.0001). Pairs of readers gave scores within 1 point for the chronicity index and within 2 points for the activity index in 50% of cases, and risk group assignments based on chronicity index (three strata) and activity index (two strata) were concordant in 59% and 76% of cases, respectively. Intraclass correlation coefficients for inter-reader agreement were 0.58 for the chronicity index (P < 0.01) and 0.52 for the activity index (P < 0.01). Intrareader agreement was uniformly higher than inter-reader agreement, but mean intraclass correlation coefficients exceeded 0.70 for only 1 of the 10 index components. Repeated readings yielded chronicity index scores that were more than 1 point discordant in 45% of cases and activity index scores that were more than 2 points discordant in 43% of cases. Risk group assignment changed on the basis of chronicity index and activity index in 36% and 21% of cases, respectively.In a nonreferral setting, the NIH-modified scoring system for lupus nephritis is only moderately reproducible and, if used to prognosticate renal outcome, may result in erroneous predictions of risk for renal failure and response to therapy.
Beginning a Career in Pediatric Hematology: 1926
Authors: Mila I. Pierce Rhoads
Journal: JAMA (1988)

Since retiring, I've been asked several times what it was like when I went to medical school. Was it hard being a woman physician? How did you know you wanted to be a pediatrician? Why did you work with children who had cancer? And, since leukemia was surely a fatal disease at the time, why did you choose to work with those children? The answers to all these questions are complex and I have found them difficult to answer briefly. It was true that less than 10% of the freshman medical class of 1925 were women, but they were wonderful, lasting friends, as were many of the men. Medical school seemed no more difficult for the women in our class than for the men, who were always ready to do thoughtful things such as pith my frog in zoology or invite me to a class dance. How did I decide
Antihypertensive Therapy and Reduced Life-Insurance Premiums
Authors: WILLIAM J. MROCZEK
Journal: Annals of Internal Medicine (1978)

Editorials1 May 1978Antihypertensive Therapy and Reduced Life-Insurance PremiumsWILLIAM J. MROCZEK, M.D.WILLIAM J. MROCZEK, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-88-5-706 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThat hypertension is associated with a large increase in morbidity and mortality from various causes is well known. Even minimal elevations of arterial blood pressure have a strong effect on life expectancy. It is not surprising that much of the information on this excess in morbidity and mortality has been assembled by insurance actuaries (1). The large effect of even a small increase in blood pressure can be seen in the estimate that a 35-year-old man with a blood pressure of 150/100 mm Hg will have a shorter life by 16.5 years if his hypertension remains untreated (1). Not surprisingly...References1. Build and Blood Pressure Study, Vol. 1. Chicago, Society of Actuaries, 1959 Google Scholar2. The Underwriting Significance of Hypertension for the Life Insurance Industry. DHEW Publication No. (NIH) 74-426. Bethesda, U.S. Department of Health, Education, and Welfare, 1974 Google Scholar3. : Effects of treatment on morbidity in hypertension. I. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA 202:1028-1034, 1967 CrossrefMedlineGoogle Scholar4. : Effects of treatment on morbidity in hypertension. II. Results in patients with diastolic blood pressures averaging 90 through 114 mm Hg. JAMA 213:1143-1152, 1970 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: WILLIAM J. MROCZEK, M.D.Affiliations: Howard University Medical Service D.C. General Hospital Washington, D.C. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1978Volume 88, Issue 5Page: 706-707KeywordsAntihypertensive drug therapyBlood pressureHypertensionLife expectancyMorbidityMortality ePublished: 1 December 2008 Issue Published: 1 May 1978 PDF downloadLoading ...
CHRONIC PULMONARY MILIARY TUBERCULOSIS
Authors: BARNETT P. STIVELMAN
Journal: JAMA (1923)

The pulmonary form of acute miliary tuberculosis is admittedly the most rapidly fatal of all types of phthisical lesions. Its diagnosis does not as a rule present many difficulties because the marked prostration, cyanosis and dyspnea, which are apparently out of all proportion to the scant signs in the chest, constitute a veritable diagnostic triad. The roentgen-ray findings in such cases may at first be inconclusive; but, before long, the appearance of the characteristic diffuse dissemination of the miliary tubercles dispels any doubt as to the true nature of the process. A form of chronic pulmonary tuberculosis is not infrequently observed in which the miliary tubercles appearing in large numbers is an important element in the lesion. These may be confined to the upper lobes, but are most commonly found in the lower lobes. It is only rarely that one finds a chronic case in which the miliary tubercles are
Case 33-1984
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely
Journal: New England Journal of Medicine (1984)

Presentation of Case A 75-year-old woman was admitted to the hospital because of lumbar pain. She was well until nine months earlier, when gross hematuria and dysuria developed. The hematuria resolved after the administration of trimethoprim–sulfamethoxazole. She came to this hospital, and an intravenous urographic examination showed a normal appearance of the kidneys except for a crossing renal vessel that indented the right renal pelvis; both ureters appeared normal; a lobulated mass, 2 cm, was observed on the left lateral wall of the bladder. She was admitted to the hospital. There was a 25-year history of diabetes mellitus, managed with . . .
Scrotal Lymphocele Diagnosis by Lymphoscintigraphy
Authors: GEORGE CHACKO, LARRY PENNINGTON, JULIE ALFORD, JOE C. LEONARD
Journal: Clinical Nuclear Medicine (1995)

Lymphocele formation is a recognized postoperative complication of renal transplantation, and diagnostic confirmation can be difficult. Although their detection as a photopenic defect during renal imaging has been previously reported, differentiation from a urinoma has required aspiration and biochemical confirmation. The authors believe the present case represents the first case, initially suspected during renal imaging, to be demonstrated by lymphoscintigraphy.
The pattern of response to interferon alpha (α-IFN) predicts sustained response to a 6-month α-IFN and ribavirin retreatment for chronic hepatitis C
Authors: Luisa Cavalletto, Liliana Chemello, Carlo Donada, Pietro Casarin, Fabio Belussi, Elisabetta Bernardinello, Filippo Marino, Patrizia Pontisso, Angelo Gatta, Alfredo Alberti
Journal: Journal of Hepatology (2000)