tbuckley/cabot-search huggingface dataset:
Transfection of Dendritic Cells with in Vitro-Transcribed CMV RNA Induces Polyclonal CD8+- and CD4+-Mediated CMV-Specific T Cell Responses
Authors: Annkristin Heine, Frank Grünebach, Tobias Holderried, Silke Appel, Markus M. Weck, Daniela Dörfel, Christian Sinzger, Peter Brossart
Journal: Molecular Therapy (2005)

Transfection of dendritic cells (DCs) with RNA was shown to be effective in the generation of antigen-specific T cells, probably due to the induction of a polyclonal T cell response directed against multiple antigens. To verify this assumption we used DCs, generated from cytomegalovirus (CMV)-negative or -positive donors, that were electroporated with in vitro-transcribed RNA (in vitro transcript, IVT) coding for the CMV pp65 antigen. We found that transfection of DCs with pp65 IVT induces an expansion of polyclonal CD8+ T lymphocytes that recognize peptide antigens presented on different HLA molecules. These T lymphocytes are able to lyse DCs pulsed with pp65-derived peptides or transfected with the cognate IVT. Furthermore, this approach allowed the identification of immunodominant epitopes presented upon IVT transfection. Interestingly, transfection of DCs with pp65 IVT resulted in the induction of CD4+-specific T cells. Cotransfection of DCs with IVTs coding for the CMV antigens pp65 and IE1 elicited polyclonal T lymphocytes specific for peptides derived from both antigens. More importantly, cytotoxic T cells could be generated in two of three CMV-negative donors. Finally, functional CMV-specific autologous cytotoxic T lymphocytes were successfully generated from immunosuppressed patients after allogeneic hematopoietic stem cell transplantation.
Re: Fritz H. Schröder, Jonas Hugosson, Sigrid Carlsson, et al. Screening for Prostate Cancer Decreases the Risk of Developing Metastatic Disease: Findings from the European Randomized Study of Screening for Prostate Cancer (ERSPC). Eur Urol 2012;62:745–52
Authors: Alain Braillon, Gérard Dubois
Journal: European Urology (2012)
The Stirling County Study of Psychiatric Disorder &amp; Sociocultural Environment. Vol I: My Name is Legion: Foundations for a Theory of Man in Relation to Culture
Authors: Marjorie C. Meehan
Journal: JAMA (1964)

For more than a decade an impressive research project to determine the prevalence of psychiatric illness and its relationships to social and cultural factors was carried out in a Canadian county. A total of 115 individuals worked on the project, as well as 31 consultants and 13 secretaries. Three large volumes and 32 other publications present the findings to date. Presumably a vast number of man-hours and dollars have been expended. It is questionable whether the results justify the effort. The first volume,<i>My Name is Legion</i>, tells about the project. Mainly, however, the director, Alexander Leighton, indicates his views on personality, psychiatric disorder, and the significance of social disintegration. In a skillful combination of illustrative examples and theoretical discussion, he presents many interesting ideas and explains the philosophy underlying the research project. The book seems overlong, perhaps because of frequent summaries and repetitions. <i>People of Cove and Woodlot</i>describes
Abstract LB-213: Plasma soluble VEGFR1 is a potential dual biomarker of response and toxicity for bevacizumab with chemoradiation in locally advanced rectal cancer
Authors: Dan G. Duda, Christopher G. Willett, Marek Ancukiewicz, Emmanuelle di Tomaso, Mira Shah, Brian G. Czito, Rex Bentley, Martin Poleski, Gregory Y. Lauwers, Madeline Carroll, Douglas Tyler, Christopher Mantyh, Paul Shellito, Jeffrey W. Clark, Rakesh K. Jain
Journal: Cancer Research (2010)

Abstract We explored plasma and urinary concentration of four members of the vascular endothelial growth factor (VEGF) family as potential response and toxicity biomarker of bevacizumab with neoadjuvant chemoradiation in patients with localized rectal cancer. The levels of VEGF, placental growth factor (PlGF) and soluble VEGF receptors 1 and −2 (sVEGFR1 and sVEGFR2) were measured by multiplex array in plasma and urine at baseline and during treatment. Pre-treatment values and changes over time were analyzed as potential biomarkers of pathological response to treatment (evaluated histologically using ypT, Mandard and N scoring at surgery) as well as for all acute toxicities in patients with locally advanced rectal cancer treated prospectively from 2002 to 2008 with bevacizumab, 5-fluorouracil and radiation therapy prior to surgery in a phase I/II trial (N=32 patients). Of all biomarkers, the pretreatment plasma sVEGFR1 - an endogenous blocker of VEGF and a factor linked with “vascular normalization” - was strikingly associated with both tumor regression and with the number of adverse events after preoperative (neoadjuvant) bevacizumab and chemoradiation. Thus, plasma sVEGFR1 is a strong candidate as the first biomarker to stratify patients for bevacizumab therapy. Therefore, future studies of bevacizumab and/or cytotoxics should be further explore sVEGFR1 as biomarker in neoadjuvant setting as well as in metastatic disease. This study was partially supported by NIH grants R21-CA99237, P01-CA80124, R01-CA115767, R01-CA85140, R01-CA126642 and Federal Share/NCI Proton Beam Program Income grants, and by the National Foundation for Cancer Research. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-213.
Seriously ill elderly patients are subjected to futile endoscopies
Authors: Susan Mayor
Journal: BMJ (2004)

<h3>ABSTRACT</h3> Type 1 Diabetes (T1D) is an autoimmune disease characterized by destruction of pancreatic β-cells. Focusing on the main insulin epitope, insulin B-chain 9-23 (insB:9-23), we explored whether a microbial insB:9-23 mimic could modulate T1D. We now demonstrate that a microbial insB:9-23 mimic of <i>Parabacteroides distasonis,</i> a human gut commensal, exclusively stimulates non-obese diabetic (NOD) mouse T cells specific to insB:9-23. Indeed, immunization of NOD mice with either the bacterial mimic peptide or insB:9-23 further verified the cross-reactivity in vivo. Modeling <i>P. distasonis</i> peptide revealed a potential pathogenic register 3 binding. <i>P. distasonis</i> colonization of the female NOD mice gut accelerated T1D onset. In addition, adoptive transfer of splenocytes from NOD mice colonized with <i>P. distasonis</i> to NOD.SCID recipients conferred the enhanced disease phenotype. Integration analysis of published infant T1D gut microbiome data revealed that <i>P. distasonis</i> peptide is not present in the gut microbiota in the first year of life of infants that eventually develop T1D. Furthermore, <i>P. distasonis</i> peptide can stimulate human T cell clones specific to insB:9-23 and T1D patients demonstrated a strong humoral immune response to <i>P. distasonis</i> than controls. Taken together, our studies define a potential molecular mimicry link between T1D pathogenesis and the gut microbiota. <h3>One Sentence Summary</h3> The human gut commensal bacterium, <i>Parabacteroides distasonis,</i> accelerates type 1 diabetes in the NOD mouse model of the disease and involves expression of an insulin B:9-23 epitope mimic, supporting a potential disease mechanism involving molecular mimicry.
Tuberculous Addison's disease and thyrotoxicosis
Authors: C. P. Casten
Journal: JAMA (1978)

Addison's disease developed in two patients after they had tuberculosis. Thyrotoxicosis subsequently developed. In both cases, the adrenal glands were calcified, suggesting that Addison's disease was tuberculous in origin. Results of tests for antihyroglobulin, antimicrosomal, and adrenal cortex antibodies were normal. These findings do not suggest an autoimmune basis for the occurrence of the two endocrinopathies. The rarity of the simultaneous occurrence of both disorders suggests it to be fortuitous.
Survival Rate After Cardiac Arrest in a Community Hospital
Authors: Raynaldo G. Sandoval
Journal: JAMA (1965)

THIS STUDY consists of a six-month survey (Aug 1, 1964, to Jan 31, 1965) of attempts at resuscitation of patients in whom cardiac arrests developed at onset or during the course of their illness. All attempts at resuscitation were done at Muhlenberg Hospital, Plainfield, NJ, a 550-bed community hospital serving a wide residential area of Union, Somerset, and Middlesex counties. Certain criteria for the diagnosis of cardiac arrests were established, as well as extent of adequate attempt at cardiac resuscitation. <h3>Criteria for Cardiac Arrests.—</h3> (1) Clinical evidence has been obtained through examination of the patients by at least three competent observers, who found the patient to have no audible heart sounds; no blood pressure, respiration, and pulse;dilated pupils; and pallor with or without cyanosis. (2) There is electrocardiographic evidence of cardiac standstill or ventricular fibrillation. <h3>Criteria for Adequate Attempt at Resuscitation. —</h3> Continuous or active external cardiac massage
Abstract A42: Small molecule activators of p53 for the treatment of inflammatory breast cancer
Authors: Namita Chatterjee, Courtney J. Ensslin, Martin P. Tenniswood
Journal: Cancer Research (2009)

Abstract Although rare, inflammatory breast cancer (IBC) is the most aggressive form of breast cancer with a 5 year survival of 40% compared to 85% for ductal carcinoma in situ. The standard therapy for this disease is chemo- and radiation therapy; however there are currently no targeted therapies for IBC. Histopathology data suggests that 40–70% of IBC tumors express wild type p53, while approximately 40% are estrogen receptor positive (ER+). The disease is characterized by early and diffuse intravasation of the breast lymphatic vessels by the tumor cells which form emboli that block the drainage of the ducts leading to swelling of the affected breast and erythema. Efforts to increase survival from this often lethal disease have been hindered by the paucity of model systems for studying the underlying biology of IBC. We have used the SUM 149PT and SUM 190PT cell lines, which were originally derived from IBC to investigate the utility of two histone deacetylase (HDAC) inhibitors (CG-1521 and TSA), alone and in combination with anti-estrogens as a novel therapy for the disease. In prostate cancer cell lines CG-1521 has been shown to acetylate p53 at Lys 373 and induce cell death, while TSA induces specific acetylation of Lys382 and induces cell cycle arrest. Both SUM 149PT and SUM 190PT express ERα and ERβ, although neither cell line requires estradiol for cell growth. SUM149PT cells express wild type p53, while the SUM 190PT express a truncated isoform of the protein. CG-1521 induces DNA fragmentation and cell death in both cell lines. While TSA also induces cell death in the SUM 149PT cells, it only induces cell cycle arrest in the SUM 190PT cells, which we attribute to the truncation of the p53 protein. Treatment of SUM149PT cells with low doses of either tamoxifen or CG-1521 individually does not induce apoptosis but in combination, causes a substantial decrease in cell number and indicates that the two compounds act synergistically in this context. These data suggest that HDAC inhibitors such as CG-1521 and TSA, which target specific Lys residues in p53 may be useful for the treatment of IBC. Citation Information: Cancer Res 2009;69(23 Suppl):A42.
Cancer: A Comprehensive Treatise, vol 1: Etiology, Chemical and Physical Carcinogenesis
Authors: John Higginson
Journal: JAMA (1982)

The last three decades have seen considerable progress in the possibilities of primary prevention of human cancer. Not only have the major causes for a number of human cancers been identified (nearly 50% in US males), but also understanding of neoplastic mechanisms has increased enormously owing to developments in biochemistry and molecular biology. Such studies have, however, emphasized the complexities of carcinogenesis, the multistage nature of which is now influencing modern conceptual approaches to cancer control. This revised second edition of the cancer series edited by Dr Becker is a useful introduction to the complexities of carcinogenesis and will be of value to young research workers who wish a broad approach. While the treatise cannot be regarded as complete, it contains useful chapters on recent developments not only in relation to classic studies on initiation, but also in relation to nonspecific modulators of carcinogenic factors and their influence on metabolic
ApoB-containing lipoproteins regulate angiogenesis by modulating expression of VEGF receptor 1
Authors: Inbal Avraham-Davidi, Yona Ely, Van N Pham, Daniel Castranova, Moshe Grunspan, Guy Malkinson, Liron Gibbs-Bar, Oded Mayseless, Gabriella Allmog, Brigid Lo, Carmen M Warren, Tom T Chen, Josette Ungos, Kameha Kidd, Kenna Shaw, Ilana Rogachev, Wuzhou Wan, Philip M Murphy, Steven A Farber, Liran Carmel, Gregory S Shelness, M Luisa Iruela-Arispe, Brant M Weinstein, Karina Yaniv
Journal: Nature Medicine (2012)
Harvesting organs from recently executed prisoners
Authors: H. Hillman, V. Nathanson
Journal: BMJ (2001)

Editor—On 27 June 2001 Thomas Diflo, a New York transplant surgeon, Wang Guoqui, a Chinese doctor who had taken kidneys and skin from recently executed prisoners, and Harry Wu of the Laogai Association gave evidence to the committee on international relations of the United States House of Representatives in Washington, DC. They noted that in China, organs are taken from recently executed prisoners, to be transplanted into recipients from the United States, Taiwan, Malaysia, Japan, and other countries. The recipients pay $17 000-40 000 each. It was not known whether the executed prisoners had given their consent.

In China prisoners can be executed for crimes such as rape, robbery, drug dealing, and black market activities, in addition to murder. It is extremely rare for those accused not to be found guilty. As soon as the prisoners are sentenced, blood samples are taken for grouping. The prisoners' appeals are hardly ever upheld. They find this out only when they are taken to be shot. Ambulances wait at the site of the executions, and the fresh organs from healthy young persons are harvested, to be transplanted into recipients from abroad.

The World Medical Association made declarations condemning these practices at Brussels in 1985 (on the grounds that this was commercial exploitation of human organs), at Madrid in 1987 (on the grounds that doctors should not participate and that it was not known if the executed prisoners had given consent to the use of their organs), and at Stockholm in 1994, when the BMA had rejoined the World Medical Association (on the same grounds as the 1987 declaration).

In Beijing, in 1998, Delon Humann, the secretary of the World Medical Association, Anders Milton, its chairman, and Dr T J Moon of the Korean Medical Association, reached an agreement with the Chinese Medical Association that these practices were undesirable and that they would investigate them jointly, with a view to stopping them. Nevertheless, in 2000, the Chinese reneged on these undertakings and refused to cooperate. This lucrative and immoral trade continues unabated. One is entitled to ask whether any British patients have visited China to receive transplant from executed prisoners, and what the international medical community can do to stop these practices?
PHYSICO-CHEMICAL FACTORS INFLUENCING EPIDERMAL DAMAGE BY SURFACE ACTIVE AGENTS
Authors: A. B. G. LANSDOWN, P. GRASSO
Journal: British Journal of Dermatology (1972)

Summary.— The responses of mouse skin to single (10%) and repeated (1% or 2·5%) applications of sodium lauryl sulphate (SLS), cetrimide and Tween‐80 were examined visually and histologically after various periods of exposure. Whereas no damage was caused by Tween‐80 when given as single applications or daily for 9 days, SLS and cetrimide both produced damage. After single applications the changes consisted of epidermal cell degeneration, focal necrosis and dermal inflammatory cell infiltration. After repeated treatment acanthosis and hyperkeratosis were identified, and nuclear debris was present in the keratin layer. Cetrimide‐treated skins were more severely damaged than those treated with SLS. In general, histological changes preceded visual changes by 1 to 2 days. Irritancy due to these surfactants was related to theri physico‐chemical properties. Since Tween‐80 at the concentrations used was highly surface active and lipophilic, these properties were not considered of importance in explaining the damage due to SLS or centrimide. Both of these agents react well with protein such as keratin whereas Tween‐80 does not. Thus it would seem that this property is of primary importance in the production of damage.
Paternal-maternal effects on phenotypic characteristics in spontaneously diabetic Nagoya-Shibata-Yasuda mice
Authors: Hironori Ueda, Hiroshi Ikegami, Yoshihiko Kawaguchi, Tomomi Fujisawa, Koji Nojima, Naru Babaya, Kazunori Yamada, Masao Shibata, Eiji Yamato, Toshio Ogihara
Journal: Metabolism (2000)
Arterial-venous relationships in the human left ventricular myocardium: anatomic basis for countercurrent regulation of blood flow.
Authors: G M Hutchins, G W Moore, E V Hatton
Journal: Circulation (1986)

The mechanism by which myocardial blood flow varies in response to metabolic demand is obscure. One hypothesis is a countercurrent regulation of arterial caliber by diffusible substances carried in venous blood. To study the anatomic basis for blood flow regulation, we performed combined arterial and venous injections in 20 human hearts and studied left ventricular intramyocardial vessels with radiography, 100 micron thick sections, and reconstructions of serial histologic sections. Penetrating arteries lie in interstitial spaces and are closely related to accompanying veins. These interstitial veins partially surround and are indented by branch arteries. A second system of veins lies within muscle fascicles between interstitial spaces and is not related to arteries. The isolated veins have collateral connections with interstitial veins and join them in the subepicardium. This vascular anatomy could allow arterial caliber to be regulated by diffusible substances carried in the interstitial veins. Arterial dilatation might prolong this effect by partial obstruction of interstitial veins, with the isolated venous system providing an alternative pathway for venous drainage and washout. The study shows that a vascular arrangement is present in human left ventricular myocardium that could provide a countercurrent regulation of blood flow with diffusible substances carried in venous blood.
John Alexander Barlas
Authors: P. Barlas
Journal: BMJ (2003)

Former general practitioner Tonbridge, Kent (b 1921; q St Thomas's Medical School, London, 1944; TD, MRCGP), died on 4 July 2003 following a severe stroke.

John Barlas joined the Royal Army Medical Corps during the second world war and served for three years in west Africa. For a short spell he was medical officer on a troopship. In late 1948 he entered general practice in Eastbourne, transferring in 1951 to a practice in Tonbridge, where he stayed until retiring at 60. He then worked part time in a Sevenoaks practice until he was 66. He was a regular supporter of the West Kent Hunt, riding his two beloved horses, and he served as regimental medical officer to the West Kent Regiment for more than 15 years. He leaves a wife, Pamela; two daughters; and four grandchildren.
Cellular mechanisms of differential action potential duration restitution in canine ventricular muscle cells during single versus double premature stimuli.
Authors: Y Kobayashi, W Peters, S S Khan, W J Mandel, H S Karagueuzian
Journal: Circulation (1992)

BACKGROUND We tested the hypothesis that action potential duration (APD) restitution of normal ventricular muscle cells is different during double premature stimuli (S3) compared with a single premature stimulus (S2). We propose a possible ionic mechanism for such a difference. METHODS AND RESULTS Action potentials and isometric tension were recorded simultaneously from isolated canine right ventricular trabeculae (2 x 2 x 10 mm) (n = 35). APD and tension restitution curves (APD) and peak tension versus diastolic interval [DI] of S2 and S3 were constructed by the extrastimulus method during pacing at 1,500 msec. The following results were obtained. 1) The APD restitution curve of S2 was different from that of S3. During the restitution of S2, an early biphasic upward hump was present at short DIs. In contrast, a smooth exponential rise was consistently seen during S3 restitution. 2) Peak tension remained significantly (p less than 0.001) lower during the restitution of S2 than during S3 restitution at all DIs tested. 3) The variation of APD during the initial 100 msec of DI was significantly longer during S3 than S2 (22 +/- 5 msec versus 41 +/- 5 msec, p less than 0.001). 4) Caffeine (2 mM, n = 5) and ryanodine (10 microM, n = 5) blocked cyclic variations of tension, presumably by blocking cyclic variations of intracellular calcium ion concentrations ([Ca2+]i), and eliminated the differences in APD restitution between S2 and S3. 5) Nisoldipine at high (5 microM) but not at lower (2 microM, n = 5) concentration eliminated the differences in restitution of both APD and tension between S2 and S3. 6) BAY K 8644 (100 nM, n = 5) had no effect on this difference. CONCLUSIONS Greater variations of APD occur during the restitution of S3 than during S2 at short DIs. These differences appear to be caused by cyclic variations in tension and thus in [Ca2+]i. Calcium-sensitive outward currents could explain these differences in APD restitution.
Psychotherapeutic Outcome: Measuring Reliable Clinical Change
Authors: Maarten Dormaar, Chantal I.M. Dijkman, Marten W. de Vries
Journal: Psychotherapy and Psychosomatics (1988)

Psychotherapeutic research is generally carried out to investigate the effectiveness of specific techniques with selected, often homogeneous samples of patients. This leads to problems when applying research findings to the clinical reality where the patient population is heterogeneous. In this study, we examine psychotherapy outcome in a natural treatment setting using criteria established by Jacobson and his colleagues for measuring improvement in psychotherapy, reliable change and clinical significance. Outcome was evaluated in a sample of 117 Dutch ambulatory mental health center patients with the SCL-90 Symptom Checklist and the Target Complaints List. On both instruments improvement rates varied greatly and were only moderately correlated. Our findings suggest that a more limited application of the Jacobson criteria derived from selected samples is warranted when applied in a general patient population.
Tuberculosis and the Acquired Immunodeficiency Syndrome in Prisoners
Authors: M. Miles Braun
Journal: JAMA (1987)

<h3>To the Editor.—</h3> Recent studies<sup>1-3</sup>have shown high rates of tuberculosis in selected patients with the acquired immunodeficiency syndrome (AIDS). A review of AIDS cases among inmates in New York State Department of Correctional Services facilities using the AIDS and tuberculosis registries has shown tuberculosis in 22 (6.9%) of 319 patients with AIDS. Four of the AIDS patients with tuberculosis were diagnosed with AIDS in 1983, three in 1984, four in 1985, and 11 in 1986 (through December). <h3>Study.—</h3> All of the AIDS patients with tuberculosis were male intravenous drug abusers, and one of them was also bisexual. Ten of the patients had extrapulmonary tuberculosis at the time of diagnosis: three lymphatic, two disseminated, two pleural, one meningeal, one peritoneal, and one hepatic. The date of the procedure diagnostic of tuberculosis preceded the date of AIDS diagnosis in 13 (59%) cases, occurred in the same month in seven cases