tbuckley/cabot-search huggingface dataset:
Allosuppressor and allohelper T cells in acute and chronic graft-vs-host disease. V. F1 mice with secondary chronic GVHD contain F1-reactive allohelper but no allosuppressor T cells.
Authors: S T Pals, H Gleichmann, E Gleichmann
Journal: The Journal of Experimental Medicine (1984)

We studied the alloreactive properties of donor T cells obtained from F1 mice that had recovered from the allosuppression of acute graft-vs.-host disease (GVHD) and showed mild symptoms of chronic GVHD, i.e., so-called secondary chronic GVHD. To this end, we used (B10 x DBA/2)F1 mice that had been injected with 10(8) B10 spleen cells 100-150 d previously. Such GVHD F1 mice were repopulated by lympho-hematopoietic cells of donor (B10) origin, which exhibited split tolerance towards the host: Whereas F1-specific donor T helper (Th) cells as well as T cells proliferating in the mixed lymphocyte reaction were readily demonstrable, F1-specific T suppressor (Ts) and T killer (Tk) cells were not, or were hardly, detectable; responses against third-party alloantigens were normal. Upon adoptive transfer to nonirradiated secondary recipients, the B10 cells obtained from the repopulated GVH F1 mice induced F1-specific enlargement of the draining popliteal lymph node and enhancement of the IgG formation therein. B10 cells of the same kind were unable, however, to induce lethal GVHD upon transfer to 950 rad-irradiated secondary (B10 x DBA/2)F1 recipients. We conclude that alloactivated donor Ts/Tk cells disappear from the host at a relatively early stage of GVHD, i.e., at the end of acute GVHD , presumably because they are short-lived. By contrast, the longevity of alloactivated donor Th cells causes the symptoms of secondary chronic GVHD.
Serum gastrin concentration affects the self replication rate of the enterochromaffin like cells in the rat stomach.
Authors: Y Tielemans, J Axelson, F Sundler, G Willems, R Hakanson
Journal: Gut (1990)

The influence of antrectomy and antrum exclusion on the enterochromaffin like cell kinetics in the gastric mucosa of the rat was studied using a combination of histamine immunocytochemistry and autoradiography after in vivo labelling with tritiated thymidine. In all experimental groups, the enterochromaffin like cells were found to incorporate the DNA precursor, thus indicating an ability to divide. The serum gastrin concentration was raised by antrum exclusion and reduced by antrectomy. After antrum exclusion, the enterochromaffin like cell proliferation rate increased as indicated by a doubling of the labelling index and by the resulting enterochromaffin like cell hyperplasia (after six weeks). After antrectomy, the enterochromaffin like cell labelling index decreased to reach 25% of the control value; at this time the enterochromaffin like cell density had not decreased significantly. The observed correlation between the enterochromaffin like cell labelling indices and the serum gastrin concentration supports the hypothesis that enterochromaffin like cell proliferation is influenced by serum gastrin.
P2-192: ERCC1 Expression is one of prognostic factors in completely resected non small-cell lung cancer patients with an adjuvant platinum-based chemotherapy
Authors: Kazuya Kondo, Haruhiko Fujino, Hiromitsu Takizawa, Takanori Miyoshi, Yukiko Hirose, Taeko Nagao, Yasushi Nakagawa, Hiroaki Toba, Mitsuteru Yoshida, Koichiro Kenzaki, Shoji Sakiyama, Akira Tangoku
Journal: Journal of Thoracic Oncology (2007)
Analysis of genomic aberrations and gene expression profiling identifies novel lesions and pathways in myeloproliferative neoplasms
Authors: K L Rice, X Lin, K Wolniak, B L Ebert, W Berkofsky-Fessler, M Buzzai, Y Sun, C Xi, P Elkin, R Levine, T Golub, D G Gilliland, J D Crispino, J D Licht, W Zhang
Journal: Blood Cancer Journal (2011)

Polycythemia vera (PV), essential thrombocythemia and primary myelofibrosis, are myeloproliferative neoplasms (MPNs) with distinct clinical features and are associated with the JAK2V617F mutation. To identify genomic anomalies involved in the pathogenesis of these disorders, we profiled 87 MPN patients using Affymetrix 250K single-nucleotide polymorphism (SNP) arrays. Aberrations affecting chr9 were the most frequently observed and included 9pLOH (n=16), trisomy 9 (n=6) and amplifications of 9p13.3–23.3 (n=1), 9q33.1–34.13 (n=1) and 9q34.13 (n=6). Patients with trisomy 9 were associated with elevated JAK2V617F mutant allele burden, suggesting that gain of chr9 represents an alternative mechanism for increasing JAK2V617F dosage. Gene expression profiling of patients with and without chr9 abnormalities (+9, 9pLOH), identified genes potentially involved in disease pathogenesis including JAK2, STAT5B and MAPK14. We also observed recurrent gains of 1p36.31–36.33 (n=6), 17q21.2–q21.31 (n=5) and 17q25.1–25.3 (n=5) and deletions affecting 18p11.31–11.32 (n=8). Combined SNP and gene expression analysis identified aberrations affecting components of a non-canonical PRC2 complex (EZH1, SUZ12 and JARID2) and genes comprising a 'HSC signature' (MLLT3, SMARCA2 and PBX1). We show that NFIB, which is amplified in 7/87 MPN patients and upregulated in PV CD34+ cells, protects cells from apoptosis induced by cytokine withdrawal.
THE SUSCEPTIBILITY OF MICE TO BACTERIAL ENDOTOXINS
Authors: Russell W. Schaedler, Rene J. Dubos
Journal: The Journal of Experimental Medicine (1961)

Albino mice (Rockefeller NCS strain) raised and maintained free of ordinary bacterial pathogens, as well as of intestinal Escherichia coli and of Proteus bacilli, were found to be highly resistant to the lethal effect of bacterial endotoxins. When newborn mice of this NCS colony were nursed by foster mothers from another colony raised under ordinary conditions (SS colony from which the NCS colony was derived), they acquired the intestinal flora of the latter animals and became susceptible to the lethal effects of endotoxins. NCS adult mice could be rendered susceptible to the lethal effect of endotoxins by vaccination with heat killed Gram-negative bacilli. The susceptibility thus induced exhibited a certain degree of specificity for the bacterial strain used in vaccination. Although untreated NCS mice were resistant to the lethal effect of endotoxins, they proved exquisitively susceptible to the infection-enhancing effect of these materials. For example, 1 microg. or less of endotoxin was found sufficient to help establish a rapidly fatal septicemia with Staphylococcus aureus. Small amounts of endotoxin (1 microg. or less), administered alone, caused a marked but transient loss of weight. Vaccination with heat-killed Gram-negative bacilli or with killed BCG increased the resistance of NCS mice to the infection-enhancing effect of small amounts of endotoxin. This protective effect exhibited a certain degree of specificity for the bacterial strain from which the toxin used in the infection-enhancing test was derived. These various findings can be explained by assuming that the pathological effects of endotoxins involve at least two unrelated mechanisms; (a) a primary toxicity illustrated in this study by the loss of weight and enhancement of infection resulting from the injection of small doses of toxin; (b) an immunological reaction with lethal consequences which became manifest only in animals sensitized to the endotoxin by prior exposure to Gram-negative bacilli.
Familial glaucoma with sleep apnoea: a new syndrome?
Authors: J T Walsh, J Montplaisir
Journal: Thorax (1982)

Sleep apnoea was combined with glaucoma in five members of two generations of a family The three surviving members with heavy snoring and glaucoma with intraocular pressure maxima in the morning and a fourth with heavy snoring only all had clinical sleep apnoea. The more severe glaucoma, resistant to surgery and medication, correlated with a greater number and duration of episodes of sleep apnoea. In all those who had recordings made episodes of sleep apnoea tended to occur and be more prolonged in rapid-eye-movement sleep. Oxygen desaturation was greater in rapid-eye-movement sleep and could occur without evidence of impaired respiration. In the third generation of this family there is as yet no evidence of impaired respiration in sleep or of glaucoma.
Ghostwriters: Not Always What They Appear-Reply
Authors: Drummond Rennie
Journal: JAMA (1995)

<h3>In Reply.</h3> —We thank Dr DeBakey and Ms DeBakey for bringing their concerns to our attention. We disagree thatThe Journal's policy requiring authors to disclose substantial editing or writing assistance validates ghostwriting or ghost authorship. We agree that ghost authors should be "flushed out" of scientific publication (we prefer the phrase "fleshed out"). However, exorcising ghosts simply transfers them to another invisible dimension; it does not eliminate them. The existence of a ghostwriter does not necessitate the dysphemistic existence of a ghost author. Thus, a writer, who solely contributes to the writing of a manuscript—visibly or not—does not automatically qualify for authorship. However, some nonauthors contribute substantial work that deserves public credit and accountability, and some contribute assistance that requires them to be named as part of disclosure of conflicts of interest. Recently, authors have described their experiences with commercial companies that offer them writing and editorial assistance.
Health of the Public: The Private-Sector Challenge
Authors: Larry B. Lehman
Journal: JAMA (1996)

To the Editor.  —In response to the article by Mr Showstack and colleagues, 1 I wish to bring to the authors' attention a poorly chosen title, rather than an erroneously focused article. Health of the Public: The Private-Sector Challenge is incorrect. The  of the private sector is maximum profitability; the challenge of the public sector is to do good by doing well.  By this time, more than a decade into the era of managed care, we should have learned a number of important lessons. First, health care is a business, managed as all other businesses; second, health care is a vendor to employers (business), and idealists (physicians, academics) will not be able to compete with pragmatists (business persons, venture capitalists) until they accept the first lesson.  This is not to say that there isn't something special still left to our profession; there is. But, as I have been told, the social responsibility
The nature of the copper complexes in bile and their relationship to the absorption and excretion of copper in normal subjects and in Wilson's disease
Authors: K. O. Lewis
Journal: Gut (1973)

Copper in bile has been shown by electrophoresis to occur neither as free ions nor complexed to protein but to be associated with a component of the micellar complexes of bile. Solvent fractionation studies suggest that the bile salt components of the lecithin-bile salt complexes are the active binding agents. The effects of specific bile salts on the behaviour of copper during electrophoresis supports this possibility. The relationship of certain bile salts to the excretion of copper in man during the time that an external biliary fistula was functioning and to the intestinal absorption of copper in the rat was found to confirm this concept. The results show that copper in bile is associated with taurochenodeoxycholate and suggest an explanation for the elevated tissue copper levels found in Wilson's disease.
A5.31 The Role of BOB1 in Rheumnatoid Arthritis: Potential Implications for Autoimmunity
Authors: Nataliya Yeremenko, Tineke Cantaert, Melissa van Tok, Ioana Gofita, Juan D Canete, Paul P Tak, Hergen Spits, Dominique Baeten
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is a prototypic autoimmune disease characterised by a prominent humoral autoimmunity. Of particular relevance is the local production of autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies in the inflamed synovial tissue. The mechanisms underlying break of B cell tolerance and local autoantibody production remains poorly understood. <h3>Objectives</h3> To identify cellular and molecular pathways implicated in RA-specific humoral autoimmunity. <h3>Methods</h3> Synovial tissue samples were obtained by arthroscopy from untreated individuals with RA (n = 33) and inflammation matched SpA controls (n = 58). Gene expression profiling was performed on tissue samples of patients with established arthritis using 44K. Whole Genome Human microarrays (Agilent). Top differentially expressed genes were validated on three independent cohorts by Taqman based RT-qPCR and immunohistochemistry. Collagen-induced arthritis (CIA) and Experimental autoimmune encephalomyelitis (EAE) experiments were conducted using Bob1 knockout mice and their littermate controls. <h3>Results</h3> Microarray screening for genes differentially expressed in the inflamed synovium, the key target of the disease process in RA, revealed a prominent and disease-specific B cell/plasma cell signature with the B cell-specific transcriptional co-activator Bob1 and its transcriptional target BCMA among the most upregulated genes. Validation by RT-qPCR on two independent cohorts representing early and established arthritis confirmed microarray data and demonstrated elevated expression of Bob1 and BCMA not only in established RA, but also at the early phase of the disease. Quantitative evaluation of immunohistochemical stainings of synovial tissue with monoclonal antibody for Bob1 revealed significant increase in Bob1 positive cells in RA synovium (p &lt; 0.01). Next we determined whether lack of functional Bob1 modifies disease onset or severity in CIA. Interestingly, the results showed that Bob1<sup>−</sup><sup>/</sup><sup>−</sup> mice were fully resistant to CIA induction compared to their wild-type littermates. This remarkable protection from CIA is explained by decreased antigen-presentation/costimulatory capacity of B cells and by failure to produce pathogenic anti-collagen autoantibodies in the absence of Bob1. <h3>Conclusions</h3> The specific increase in Bob1 expressing cells in RA synovitis and the resistance of Bob1-deficient mice to development of CIA indicate that Bob1/BCMA axis may contribute to humoral autoimmunity in RA. The relationship between an aberrant Bob1 expression and the break of peripheral tolerance in RA is currently under investigation.
Disaster-Relief Anesthesia — Notes on Coming Home
Authors: Paul G Firth
Journal: New England Journal of Medicine (2010)

Anesthesiologists have a unique view of humanitarian disasters, as I discovered when I spent 21 days volunteering on the U.S.N.S. Comfort after the January earthquake in Haiti. Based in operating rooms, anesthesiologists see close up the entire grotesque flood of distorted bodies. Under pressure, we tend to cope by focusing on the mechanics of the body and the technicalities of procedures — to think not of dying or shattered people, but of damaged anatomy and the techniques of repair. After our team had done several days of intense work with patients with complicated limb wounds, broken pelvises, skull factures, and . . .
The expression of a gamma interferon-induced protein (IP-10) in delayed immune responses in human skin.
Authors: G Kaplan, A D Luster, G Hancock, Z A Cohn
Journal: The Journal of Experimental Medicine (1987)

Our knowledge of the induction of new molecules by IFN-gamma has led to the characterization of IP-10 and the preparation of a monospecific, polyclonal antibody. Using this reagent we have now examined inflammatory states occurring in human skin and used immunocytochemical staining for the expression of both Ia and IP-10 determinants. After evoking a delayed-type response to purified protein derivative of tuberculin (PPD), we noted the presence of IP-10 in dermal macrophages and endothelial cells. Intense staining of the basal layer of epidermal keratinocytes was prominent at 41 h, and by 1 wk the entire epidermis was staining. The comparison of the amount of IP-10 secreted by keratinocytes vs. macrophages, fibroblasts, and endothelial cells revealed that keratinocytes were by far the major producers of this molecule. The expression of Ia occurred in conjunction with IP-10. The injection of rIFN-gamma mimicked many of the features of the PPD response, including the expression of both Ia and IP-10 by epidermal keratinocytes. Coexpression was also found in the natural lesions of tuberculoid leprosy and cutaneous Leishmaniasis. However, it was absent in lepromatous leprosy, a state where activated T lymphocytes are not present. We suggest that the local production of IFN-gamma by T cells of the dermal infiltrate induces IP-10 formation in both the dermis and epidermis. IP-10 and Ia then serve as specific markers of immune IFN and its possible influence on effector cells of the cell mediated immune response.
Number of uninsured in the United States increases by 2.4m
Authors: S. Gottlieb
Journal: BMJ (2003)

New figures from the US Census Bureau show that 2.4 million Americans were added to the roll of uninsured people in 2002, but experts say it could have been much worse.

The number of people without health coverage rose to 43.6 million in 2002, or more than 15% of the population. The bureau's report also showed that 242.2 million Americans had health insurance last year, up 1.5 million from 2001. Many Americans lost private coverage because of …
Tumor-suppressor genes: cardinal factors in inherited predisposition to human cancers.
Authors: H J Evans, J Prosser
Journal: Environmental Health Perspectives (1992)

A predisposition to the development of certain specific and familial cancers is associated with the inheritance of a single mutated gene. In the best-characterized cases, this primary mutation is a loss of function mutation consistent with viability but resulting in neoplastic change consequent to the acquisition of a second somatic mutation at the same locus. Such genes are referred to as tumor-suppressor genes. Classical examples are the Rb-1 gene associated with the development of retinoblastoma and the p53 gene, which is associated with a wider range of neoplasms, including breast cancer. Other tumor-suppressor genes have been isolated which are associated with Wilms' tumor, neurofibromatosis, and inherited and sporadic forms of colorectal cancer. Some of these genes appear to act as negative regulators of mitotic cycle genes, and others may have different properties. The nature of these genes is discussed, as is the evidence for the involvement of tumor-suppressor genes in other inherited, and sporadic, forms of cancer. Some recent data on the Wilms' tumor gene, WT1, and on the involvement of the p53 gene in breast cancer are presented, and the importance of genomic imprinting in contributing to the excess of suppressor gene mutations in chromosomes of paternal origin is considered.
Short‐ and long‐term outcomes of intracoronary and endogenously mobilized bone marrow stem cells in the treatment of ST‐segment elevation myocardial infarction: a meta‐analysis of randomized control trials
Authors: Hendrik Zimmet, Pramote Porapakkham, Pornwalee Porapakkham, Yusuke Sata, Steven Joseph Haas, Silviu Itescu, Andrew Forbes, Henry Krum
Journal: European Journal of Heart Failure (2011)
Book Review The Western Medical Tradition, 800 B.C. to A.D. 1800 By Lawrence I. Conrad, Michael Neve, Vivian Nutton, Roy Porter, and Andrew Wear. 556 pp., illustrated. New York, Cambridge University Press, 1995. $34.95. 0-521-47564-3
Authors: Gary B. Ferngren
Journal: New England Journal of Medicine (1996)
The Nuts Among the Berries
Authors: Philip L. White
Journal: JAMA (1962)

The origin of food faddism is traced back to Elisha Perkins who in 1796 discovered the "secret of perpetual good health." It might be said that he was the first great American quack. Since that time, many others have come into prominence. The book does not try to catalogue fully every quack or faddist but merely to give the reader an informative glimpse into this overpopulated field. There are very few people at the present time who have not in some way been affected by curious nutritional concepts. During the 19th century, very little was known about human nutrition. Medicine also seemed stalemated at this time although doctors were beginning to understand more about the human body and a great body of scientific information was being built. It was during this era that people such as John Harvey Kellogg and Charles Post were able to exert such influence upon the
Recombinant Oncolytic Poliovirus Eliminates Glioma In Vivo Without Genetic Adaptation to a Pathogenic Phenotype
Authors: Elena Y Dobrikova, Trevor Broadt, Judith Poiley-Nelson, Xiaoyi Yang, Gopalan Soman, Steve Giardina, Ray Harris, Matthias Gromeier
Journal: Molecular Therapy (2008)

Many viruses, either naturally occurring or as a result of genetic manipulation, exhibit conditional replication in transformed cells. This principle is the basis for experimental therapeutic approaches exploiting the oncolytic potential of such agents without the danger of collateral damage to resistant normal tissues. One of the potential obstacles to these approaches is the possibility of genetic adaptation of oncolytic viruses upon replication in susceptible tumor tissues. Genetic variation can reverse genetic manipulations of parental viral genomes that determine attenuation of virulence, selective tumor cell tropism or other desirable traits. Alternatively, it may convey new properties not originally associated with parental strains, e.g., adaptation to a human host range. We examined genetic stability of an oncolytic nonpathogenic poliovirus recombinant considered for therapy of recurrent glioblastoma multiforme (GBM). This was done by serial passage experiments in glioma xenografts in vivo and investigation of phenotypic and genotypic markers of attenuation. Intratumoral inoculation of oncolytic poliovirus produced efficient tumor regress and elimination without altering temperature-sensitive growth, selective cytotoxicity, or genetic markers of attenuation of virus recovered from inoculated animals. Our studies demonstrate that active viral oncolysis of malignant glioma does not alter the conditional replication properties of oncolytic nonpathogenic poliovirus recombinants.