tbuckley/cabot-search huggingface dataset:
STUDIES ON ANTIGENIC COMPETITION
Authors: Neil I. Brody, Gregory W. Siskind
Journal: The Journal of Experimental Medicine (1969)

Antigenic competition was studied in a haptenic system. It was found that: (a) The extent of competition is greater when larger doses of antigen are employed. (b) Antigenic competition appears to be independent of the carrier molecule. (c) The affinity of the antibody produced in antigenic competition is approximately equal to the affinity of antibody formed by animals immunized with only one antigen. (d) Antigenic competition only occurs when both antigens are injected so as to drain into the same regional lymph nodes. The results suggest that antigenic competition occurs locally at the site of antigen stimulation and is not mediated by a circulating factor, by tolerance induction, or by suppression due to synthesis of cross-reacting antibodies.
Histone Deacetylase Inhibitor Enhances Recovery after AKI
Authors: Chiara Cianciolo Cosentino, Nataliya I. Skrypnyk, Lauren L. Brilli, Takuto Chiba, Tatiana Novitskaya, Clara Woods, James West, Vasiliy N. Korotchenko, Lee McDermott, Billy W. Day, Alan J. Davidson, Raymond C. Harris, Mark P. de Caestecker, Neil A. Hukriede
Journal: Journal of the American Society of Nephrology (2013)

At present, there are no effective therapies to ameliorate injury, accelerate recovery, or prevent postinjury fibrosis after AKI. Here, we sought to identify candidate compounds that accelerate recovery after AKI by screening for small molecules that increase proliferation of renal progenitor cells in zebrafish embryos. One compound identified from this screen was the histone deacetylase inhibitor methyl-4-(phenylthio)butanoate, which we subsequently administered to zebrafish larvae and mice 24-48 hours after inducing AKI. In zebrafish, treatment with the compound increased larval survival and proliferation of renal tubular epithelial cells. In mice, treatment accelerated recovery, reduced postinjury tubular atrophy and interstitial fibrosis, and increased the regenerative capacity of actively cycling renal tubular cells by decreasing the number of cells in G2/M arrest. These data suggest that accelerating recovery may be a viable approach to treating AKI and provide proof of concept that a screen in zebrafish embryos can identify therapeutic candidates for kidney injury.
Preconception Counseling in Women With Diabetes
Authors: Avnish Tripathi, Judith Rankin, Joan Aarvold, Colin Chandler, Ruth Bell
Journal: Diabetes Care (2009)

OBJECTIVE To investigate the association of preconception counseling with markers of care and maternal characteristics in women with pregestational diabetes. RESEARCH DESIGN AND METHODS The study includes data from a regional multi-center survey on 588 women with pregestational diabetes who delivered a singleton pregnancy between 2001 and 2004. Logistic regression was used to obtain crude and adjusted estimates of association. RESULTS Preconception counseling was associated with better glycemic control 3 months preconception (odds ratio 1.91, 95% CI 1.10–3.04) and in the first trimester (2.05, 1.39–3.03), higher preconception folic acid intake (4.88, 3.26–7.30), and reduced risk of adverse pregnancy outcome (P = 0.027). Uptake of preconception counseling was positively associated with type 1 diabetes (1.87, 1.14–3.07) and White British ethnicity (2.56, 1.17–5.6) and negatively with deprivation score (0.78, 0.70–0.87). CONCLUSIONS Efforts are needed to improve preconception counseling rates. Uptake is associated with maternal sociodemographic characteristics.
Fine Mapping Reveals Multiple Loci and a Possible Epistatic Interaction within the Mammary Carcinoma Susceptibility Quantitative Trait Locus, <i>Mcs5</i>
Authors: David J. Samuelson, Beth A. Aperavich, Jill D. Haag, Michael N. Gould
Journal: Cancer Research (2005)

Abstract To identify high-frequency, low-penetrance breast cancer modifier genes, we have developed a rat genetic model that uses the Wistar-Kyoto (WKy) inbred strain, resistant to developing 7,12-dimethylbenz[a]anthracene–induced mammary carcinogenesis, as a congenic donor and the susceptible Wistar-Furth (WF) strain as the recipient. Here, data from congenic rat lines containing smaller WKy genomic intervals of the Mcs5 quantitative trait locus region are presented to fine map three independently acting Mcs5 subloci. WKy-homozygous females from congenic lines defining Mcs5a, Mcs5b, and Mcs5c averaged, respectively, 4.0 ± 0.4, 11.6 ± 0.6, and 3.5 ± 0.4 mammary carcinomas per rat. These phenotypic values are statistically different from the WF-homozygous phenotype value of 8.0 ± 0.4, which is the baseline phenotype used for these experiments. We identified a likely Mcs5a × Mcs5b epistatic interaction that results in masking the increased susceptibility effect of the Mcs5b WKy allele by the Mcs5a WKy allele. We also provide evidence for a Mcs5a × Mcs5c interaction that is synergistic to decrease mammary carcinoma susceptibility below the additive effects of WKy alleles at each locus independently. The Mcs5 subloci are currently localized to 1.0, 7.5, and 4.5 Mb of rat chromosome 5, and the orthologous regions are on human chromosome 9 and mouse chromosome 4. These loci will provide unbiased candidate gene loci for evaluation in human case-control association studies.
Cardiac output-O2 uptake relation during incremental exercise in patients with previous myocardial infarction.
Authors: A Koike, M Hiroe, H Adachi, T Yajima, H Itoh, T Takamoto, K Taniguchi, F Marumo
Journal: Circulation (1992)

The cardiac output-O2 uptake (VO2) relation, which is thought to be linear and predictable in normal humans, has not been clarified in cardiac patients. We evaluated the relation between cardiac output and VO2 during the incremental exercise test in patients with previous myocardial infarction.Twenty-two patients (age, 58.1 +/- 8.0 years) with previous myocardial infarction performed a symptom-limited exercise test on a cycle ergometer. VO2 was calculated from the expired gas analysis, and cardiac output was measured by a computerized cadmium telluride detector every 10 seconds during exercise. The ratio of increase in VO2 to the increase in work rate (delta VO2/delta WR) below and above the anaerobic threshold (AT) was 11.1 +/- 3.6 and 11.1 +/- 2.9 ml/min/W, respectively, showing no significant difference. However, the ratio of increase in cardiac output to increase in work rate (delta CO/delta WR) below the AT was 50.1 +/- 26.6 ml/min/W and was significantly decreased to 11.8 +/- 25.3 ml/min/W above the AT (p = 0.0002). The decreased delta CO/delta WR above the AT primarily would be due to silent myocardial ischemia produced by exercise, as there was the presence of 201Tl redistribution in 15 of 16 patients in whom myocardial 201Tl scintigraphy with dipyridamole or exercise stress testing was evaluated. delta CO/delta VO2, which has been reported to be approximately 5.5 in normal subjects, was only 4.4 +/- 2.6 at work rates below the AT and was decreased to 1.1 +/- 2.3 at work rates above the AT.The relation between cardiac output and VO2 during exercise in patients with previous myocardial infarction differs profoundly from that reported in normal subjects. These findings must be considered when we noninvasively estimate the change in cardiac output during exercise by obtaining VO2 in patients with coronary artery disease.
Urgent Need for a New Staging System in Advanced Colorectal Cancer
Authors: Graeme J. Poston, Joan Figueras, Felice Giuliante, Gennaro Nuzzo, Alberto F. Sobrero, Jean-Francois Gigot, Bernard Nordlinger, Rene Adam, Thomas Gruenberger, Michael A. Choti, Anton J. Bilchik, Eric J.D. Van Cutsem, Jy-Ming Chiang, Michael I. D'Angelica
Journal: Journal of Clinical Oncology (2008)

Despite recent advances in the medical treatment of metastatic colorectal cancer (mCRC), which include irinotecan- and oxaliplatin-based first-line regimens, the concept of planned sequential therapy involving three active agents during the course of a patient's treatment and the increasing use of targeted monoclonal antibodies, 5-year survival rates for patients with advanced CRC remain unacceptably low. For patients with CRC liver metastases, liver resection remains the only chance of cure, with 5-year survival rates ranging from 25% to 40%. However, 80% to 85% of patients with stage IV CRC have liver disease which is considered unresectable at presentation. The rapid expansion in the use of improved combination chemotherapy regimens plus or minus biologics, to render initially unresectable metastases resectable has increased the percentage of patients eligible for potentially curative surgery. However, the current staging criteria for CRC patients with metastatic disease do not reflect these recent changes or the fact that there is also a large variation in the survival of patients with stage IV CRC. For example the survival for a patient with a solitary, resectable liver metastasis is better than that for a patient with stage III disease. A new staging system is therefore needed that acknowledges both the improvements that have been made in surgical techniques for resectable metastases and the impact of modern chemotherapy on rendering initially unresectable CRC liver metastases resectable, while at the same time distinguishing between patients with a chance of cure at presentation and those for whom only palliative treatment is possible.
HISTORICAL NOTES ON SCABIES, WITH REMARKS ON THE PALAEONTOLOGY OF THE ACARUS.
Authors: GEORGE PERNET
Journal: British Journal of Dermatology (1925)

Journal Article HISTORICAL NOTES ON SCABIES, WITH REMARKS ON THE PALÆONTOLOGY OF THE ACARUS. Get access GEORGE PERNET, M.D. GEORGE PERNET, M.D. Consulting Dermatologist, West London Hospital, and late Lecturer on Dermatology in the Post‐Graduate Medical College Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 37, Issue 7, 1 July 1925, Pages 312–316, https://doi.org/10.1111/j.1365-2133.1925.tb10004.x Published: 01 July 1925
Anticancer Chemotherapy Inhibits MHC Class I–Related Chain A Ectodomain Shedding by Downregulating ADAM10 Expression in Hepatocellular Carcinoma
Authors: Keisuke Kohga, Tetsuo Takehara, Tomohide Tatsumi, Takuya Miyagi, Hisashi Ishida, Kazuyoshi Ohkawa, Tatsuya Kanto, Naoki Hiramatsu, Norio Hayashi
Journal: Cancer Research (2009)

Abstract MHC class I–related chain A (MICA) is a ligand for the NKG2D-activating immunoreceptor that mediates activation of natural killer (NK) cells. The ectodomain of MICA is shed from tumor cells, which may be an important means of evading antitumor immunity. We previously reported that patients with hepatocellular carcinoma (HCC) display high levels of soluble MICA in circulation, which could be downregulated by chemotherapy. The present study shows that anti-HCC drugs suppress MICA ectodomain shedding by inhibiting expression of a disintegrin and metalloproteinase 10 (ADAM10). Both ADAM10 and CD44, a typical substrate of the ADAM10 protease, were expressed in human HCC tissues and HCC cells but not in normal liver tissues or cultured hepatocytes. Small interfering RNA–mediated knockdown experiments revealed that ADAM10 is a critical sheddase for both MICA and CD44 in HCC cells. Of interest is the finding that epirubicin clearly downregulated ADAM10 expression and MICA shedding in HCC cells; its suppressive effect on MICA shedding was abolished in ADAM10-depleted cells. Epirubicin treatment also enhanced the NKG2D-mediated NK sensitivity of HCC cells. Patients with HCC had significantly higher levels of serum-soluble CD44, which correlated well with serum-soluble MICA levels, thus suggesting a close link between ADAM10 activity and MICA shedding in these patients. Soluble MICA and CD44 levels were downregulated with a significant correlation in patients treated by transarterial chemoembolization using epirubicin. In conclusion, anticancer drugs can modulate expression of ADAM10, which is critically involved in MICA ectodomain shedding. Epirubicin therapy may have a previously unrecognized effect on antitumor immunity in HCC patients. [Cancer Res 2009;69(20):8050–7]
Predominance of TH1 Response in Tumor-Bearing Mice and Cancer Patients Treated With AS 101
Authors: B. Sredni, T. Tichler, A. Shani, R. Catane, B. Kaufman, G. Strassmann, M. Albeck, Y. Kalechman
Journal: JNCI Journal of the National Cancer Institute (1996)

Several studies have recently suggested that the immune response to malignant growths is regulated by distinct patterns of type 2 cytokine production. These cytokines, regulating the cytotoxic T-lymphocyte response in patients with advanced cancers, may be associated with disease progression. Evidence suggests that the T Helper 1 (TH1) and T Helper 2 (TH2) types of reaction are reciprocally regulated in vivo. The immunomodulator AS101 (ammonium trichloro [dioxoethylene- O,O' ] tellurate) was found to stimulate mouse and human cells to proliferate and secrete a variety of cytokines. Clinical trials using AS101 on cancer patients are now in progress. The aim of this study was to evaluate the ability of AS101 to modulate TH1 and TH2 responses in tumor-bearing mice and in patients with advanced cancer. In addition, we investigated the association between the predominance of each type of response with the antitumoral effects of AS101. Mice into which Lewis lung carcinoma (3LL) had been transplanted (n = 221) and cancer patients (n = 13) were treated with AS101 on alternate days, at 10μg/mouse intraperitoneally, or for the patients, at 3 mg/m 2 intravenously. The types were sarcoma, melanoma, and colon, lung, ovarian, and renal cancers. Cytokine levels were determined by immunoassay kits and compared with the paired Student's t test: in mice, they were tested in spleen cell supernatants; in humans, in sera and mononuclear cell supernatants. The chi-squared test was used to compare tumor volumes. All P values represent two-sided tests of statistical significance. Our results show that treatment of mice and patients with AS101 results in a clear predominance in TH1 responses, with a concomitant decrease in the TH2-type response. This was reflected by a significant enhancement in interleukin 2 (IL-2) and interferon gamma (IFN γ) levels ( P <.01) paralleled by a substantial decrease in IL-4 and IL-10 ( P <.01). Moreover, the concentration of IL-12 was significantly increased ( P <.01) in AS101-treated patients who also showed enhanced levels of natural and lymphokine-activated killer cell-mediated cytotoxicity. The statistically significant increases in IL-2 and IFN γ levels, paralleled by the pronounced decrease in IL-4 and IL-10 in the AS101-treated mice, were associated with its antitumoral effects. In addition, systemic contreatment of 3LL-transplanted mice with AS101 and anti-IL-12 antibodies partly abrogated the antitumoral effect of AS101. Immunotherapy with AS101 enhances TH1 function while interfering with the TH2 response. This TH1 trend may be related to the antitumor effects of AS101. Isolation and characterization of a distinct cytokine pattern in patients with advanced cancer treated with AS101 may contribute to the development of intervention strategies using this compound. [J Natl Cancer Inst 1996; 88: 1276–84]
α-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy
Authors: Jens Mogensen, Ib C. Klausen, Anders K. Pedersen, Henrik Egeblad, Peter Bross, Torben A. Kruse, Niels Gregersen, Peter S. Hansen, Ulrik Baandrup, Anders D. Børglum
Journal: Journal of Clinical Investigation (1999)

We identified the α-cardiac actin gene (ACTC) as a novel disease gene in a pedigree suffering from familial hypertrophic cardiomyopathy (FHC). Linkage analyses excluded all the previously reported FHC loci as possible disease loci in the family studied, with lod scores varying between –2.5 and –6.0. Further linkage analyses of plausible candidate genes highly expressed in the adult human heart identified ACTC as the most likely disease gene, showing a maximal lod score of 3.6. Mutation analysis of ACTC revealed an Ala295Ser mutation in exon 5 close to 2 missense mutations recently described to cause the inherited form of idiopathic dilated cardiomyopathy (IDC). ACTC is the first sarcomeric gene described in which mutations are responsible for 2 different cardiomyopathies. We hypothesize that ACTC mutations affecting sarcomere contraction lead to FHC and that mutations affecting force transmission from the sarcomere to the surrounding syncytium lead to IDC.
The Results of Raising the Resectability Rate in Operations for Lung Carcinoma
Authors: R. A. Smith
Journal: Thorax (1957)

Where obviously involved glands or tumour in the atrium appeared to be completely resected with the main mass of growth, the operation was con- sidered, for comparative purposes, to give a chance of cure and to be therefore curative in nature.Classifying into the two groups as defined, 95 were curative and 48 palliative operations.Such a on July 14,
Smoking cessation – What determines adherence to pharmacological treatment
Authors: Ana Castro, Júlia Valério, Albertina Correia, Miguel Guimarães, Ivone Pascoal
Journal: European Respiratory Journal (2011)

Introduction:  Cigarette smoking is the 1st modifiable risk factor for premature morbidity and mortality. Treating smokers is the best cost-effectiveness health care intervention.   Objective:  Assess adherence to pharmacological treatment and factors influencing it. Correlate variables determining adherence and results at the end of treatment and 12 months follow up.   Methods:  Characterization of a patients sample whom was prescribed Varenicline or Nicotine Replacement Therapy (NRT). Analyse and correlate treatment adherence with factores affecting adherence (motivation, dependency, household smoking habits, side-effects,etc).   Results:  166 smokers were included, 71%male, 28%female, mean age 49 years. Mean tabagic burden: 45pack-years. Mean motivation 8.1–Richmond test (RT); mean dependence 5,1–Fagerstrom test (FT). Varenicline was proposed to 48%and NRT to51%. 55%of patients followed the treatment correctly and the others discontinued therapy. Reasons given for non-compliance: unrecognized therapeutic effect, excessive self-confidence, price, side effects. The patients that completed treatment, 52%did not smoke at the end of treatment and 55%were nonsmokers at the end of 12 months follow up. There was a positive correlation (Spearman Correlation,p   Conclusion:  Treatment adherence is a key factor for smoking abstinence. In our group, adherence was higher in patients treated with NRT, better-educated and more motivated. False expectations, side effects and price can influence adherence to therapy. The smoking habits of the household and the degree of dependency negatively affect adherence and abstinence.
Pre-eclampsia and expression of heparin-binding EGF-like growth factor
Authors: Richard E Leach, Roberto Romero, Yeon Mee Kim, Tinnakorn Chaiworapongsa, Brian Kilburn, Sanjoy K Das, Sudhansu K Dey, Anthony Johnson, Faisal Qureshi, Suzanne Jacques, D Randall Armant
Journal: The Lancet (2002)
SPECIAL ARTICLE
Authors: ROBERT L. DEHAAN
Journal: Circulation (1967)

It is no longer necessary to guess at why embryonic malformations occur. Techniques are now available to test almost any hypothesis concerning developmental phenomena. These include the entire armamentarium of modern cell biology: organ and tissue culture, microsurgery, time-lapse cinematography, autoradiography, and many other related methodologies. The developmental events which lead to the formation of a functional heart in the early embryo can be analyzed with these techniques. Of the pertinent questions concerning developmental processes related to congenital heart disease, those of dextrocardia and differential growth, ventricular septal defects, and cell migration and adhesion in cardiogenesis are discussed. Several experimental systems useful for attacking these questions are described. Relative growth of specific segments of the primitive tubular heart contributed by the right and left wings of the cardiogenic crescent has been examined to elucidate the mechanism of dextral looping of the tube. Migration of precardiac cells to form the heart has been traced with cinematography in the intact embryo, and by following movements of cells labeled in situ with tritium using autoradiographic techniques. To analyze the mechanisms of guidance of such cells, endoderm plus adherent precardiac mesoderm can be explanted and manipulated in tissue culture.
Functional Deletion Mutation of the 5′-Flanking Region of Type A Human Natriuretic Peptide Receptor Gene and Its Association With Essential Hypertension and Left Ventricular Hypertrophy in the Japanese
Authors: Tomohiro Nakayama, Masayoshi Soma, Yukie Takahashi, Duolikun Rehemudula, Katsuo Kanmatsuse, Kiyohide Furuya
Journal: Circulation Research (2000)

Abstract —The natriuretic peptide (NP) family is involved in the regulation of blood pressure and fluid volume. We isolated the 5′-flanking region of the type A human NP receptor gene and identified an insertion/deletion mutation in this region. We then assessed whether there is a genetic association between this mutation and essential hypertension (EH). The deletion allele lacks 8 nucleotides and alters binding sites for the activator protein-2 (AP-2) and Zeste transcriptional factors. We genotyped 200 EH and 200 normotensive (NT) individuals and found 9 subjects with the deletion (8 in the EH group and 1 in the NT group). All 9 individuals were heterozygous. The NT subject with the mutation had left ventricular hypertrophy without hypertension. Transcriptional activity of the deletion allele was &lt;30% that of the wild-type allele. The plasma levels of brain NP in EH patients with the deleted allele were significantly higher than the levels in the EH patients with the wild-type allele, and plasma brain NP levels were significantly higher in subjects with the deleted allele than in subjects with the wild-type allele, despite comparable blood pressures. These findings suggest that in Japanese individuals, this deletion in the human NP receptor gene reduces receptor activity and may confer increased susceptibility to developing EH or left ventricular hypertrophy.
MECHANISMS OF IMMUNOLOGIC INJURY OF RAT PERITONEAL MAST CELLS
Authors: K. Frank Austen, Elmer L. Becker
Journal: The Journal of Experimental Medicine (1966)

There is an absolute requirement for C'1, C'2, C'4, C'3, and C'5 in releasing histamine from rat peritoneal mast cells sensitized with rabbit anti-rat gamma globulin. This conclusion is based upon the restoration of histamine-releasing capacity by adding highly purified complement components to sera deficient in one or more of these components. Of special advantage was the availability of sera from humans with inborn or acquired deficiencies in a single component. The p-nitrophenyl ethyl phosphonates block this reaction by inhibiting an antigen-antibody-activated esterase which exists in a phosphonate resistant precursor state until activated by the interaction of the sensitized mast cell and serum complement. There is almost complete disparity between the ability of the phosphonates to inhibit complement-dependent histamine release by rabbit anti-RGG and to inactivate C'1a. Even though C'1a is required for complement-dependent histamine release by rabbit anti-RGG, this is not the esterase being blocked by the phosphonates under the experimental conditions used. The pattern of inhibition by the phosphonates of the antigen-antibody-activated esterase required for complement-dependent, noncytotoxic histamine release is remarkably similar to that of the esterase required for homocytotropic antibody-mediated histamine release. One possible implication is that these two quite different modes of carrying out antigen-antibody-induced histamine release from rat peritoneal mast cells lead to activation of the same esterase and share a common pathway.