tbuckley/cabot-search huggingface dataset:
Cytotoxicity Is Mandatory for CD8+ T Cell–mediated Contact Hypersensitivity
Authors: Jeanne Kehren, Cyril Desvignes, Maya Krasteva, Marie-Thérèse Ducluzeau, Olga Assossou, Françoise Horand, Michael Hahne, David Kägi, Dominique Kaiserlian, Jean-François Nicolas
Journal: The Journal of Experimental Medicine (1999)

Contact hypersensitivity (CHS) is a T cell–mediated skin inflammation induced by epicutaneous exposure to haptens in sensitized individuals. We have previously reported that CHS to dinitrofluorobenzene in mice is mediated by major histocompatibility complex (MHC) class I–restricted CD8+ T cells. In this study, we show that CD8+ T cells mediate the skin inflammation through their cytotoxic activity. The contribution of specific cytotoxic T lymphocytes (CTLs) to the CHS reaction was examined both in vivo and in vitro, using mice deficient in perforin and/or Fas/Fas ligand (FasL) pathways involved in cytotoxicity. Mice double deficient in perforin and FasL were able to develop hapten-specific CD8+ T cells in the lymphoid organs but did not show CHS reaction. However, they did not generate hapten-specific CTLs, demonstrating that the CHS reaction is dependent on cytotoxic activity. In contrast, Fas-deficient lpr mice, FasL-deficient gld mice, and perforin-deficient mice developed a normal CHS reaction and were able to generate hapten-specific CTLs, suggesting that CHS requires either the Fas/FasL or the perforin pathway. This was confirmed by in vitro studies showing that the hapten-specific CTL activity was exclusively mediated by MHC class I–restricted CD8+ T cells which could use either the perforin or the Fas/FasL pathway for their lytic activity. Thus, cytotoxic CD8+ T cells, commonly implicated in the host defence against tumors and viral infections, could also mediate harmful delayed-type hypersensitivity reactions.
Melanocortin signaling in the CNS directly regulates circulating cholesterol
Authors: Diego Perez-Tilve, Susanna M Hofmann, Joshua Basford, Ruben Nogueiras, Paul T Pfluger, James T Patterson, Erin Grant, Hilary E Wilson-Perez, Norman A Granholm, Myrtha Arnold, James L Trevaskis, Andrew A Butler, William S Davidson, Stephen C Woods, Stephen C Benoit, Mark W Sleeman, Richard D DiMarchi, David Y Hui, Matthias H Tschöp
Journal: Nature Neuroscience (2010)
Case of Burn in a Newly-Born Infant, Resulting in Loss of the Hand
Authors: Wm. V. Bird
Journal: BMJ (1860)

linife, in the posterior part of the left thorax below the scapula, the wound not exceeding three-quarters of an inch.Some bleed- ing following, he walked to the office of a physician, who, having closed the wound with adhesive plaster, dismissed the patient, with the remark that the injury would not amount to anything.However, great oppression of breathing took place, and in eighteen hours he was a corpse.The post mortem examination, by order of the coroner, re- vealed profuse effusioin of blood into the left pleura from a wound of the intercostal artery, wvith compression of the lung.The assailant was tried for murder, anld convicted on the testimony of O'Leary's attending physician, who, with another practitioner, proved that the wound was nmortal, in spite of proper surgery, alleging that the patient could not lose blood enough from the intercostal artery, andl that the pleural sac would not hold blood sufficient to cause death.The Governor, however, on application of the friends of the condemned, had him reprieved on the testimony of several surgeons, who, uphold- ing the correctness of our conclusion, were frank to admit that, the wound not being necessarily fatal, bad surgery, and gross carelessness of management, bacl produced the death of the patient.
Rogues, Rebels, and Geniuses: The Story of Canadian Medicine
Authors: Charles G. Roland
Journal: JAMA (1982)

This book will displease many historians. It is breezy, irreverent, at times ungrammatical, and entirely without the scholarly trappings of footnotes to certify every fact. Nevertheless,<i>Rogues, Rebels, and Geniuses</i>fills a major void: it provides the nonhistorian with a highly readable introduction to some of the rich background of Canadian medicine and its practitioners. The book will be read by thousands who would not devote much time to a scholarly work on the topic, were such a work available. And it is not. A colorful cast peoples these pages—"Tiger" Dunlop, the heavy-drinking, hard-swearing Scot who helped open for settlement a large part of southern Ontario; John Christian Schultz, the fiery Manitoba physician and politician; James Barry, high-ranking British medical officer who, it is claimed (but by no means proved), was a woman; Alan Dafoe, country practitioner who delivered Mme. Dionne of her quintuplets; Emily Stowe, pioneer female physician in
Diverse effects of pinacidil on KATP channels in mouse skeletal muscle in the presence of different nucleotides
Authors: S. Hehl, B. Neumcke
Journal: Cardiovascular Research (1994)

Objective: The potassium channel opener pinacidil relaxes smooth muscle and exerts cardioprotective effects. The aim of the study was to investigate the actions of pinacidil on ATP sensitive potassium channels (KATPchannels) in mammalian skeletal muscle and to explore the interrelations of this drug with various nucleotides. Methods: Single skeletal muscle fibres were prepared enzymatically from flexor digitorum brevis muscles of adult mice. Membrane patches of the inside-out configuration were excised in a Ca2+-free solution, and currents through single KATP channels were recorded at -40 mV. The cytoplasmic face of the patch was exposed to a K+-rich solution with MgCl2 (1 mM), and pinacidil (0.1 or 0.4 mM) and the nucleotides (0.1 mM) were added to this internal solution. Results: KATP channels were not activated by pinacidil in the presence of the non-hydrolysable ATP analogue AMP-PNP, in contrast to the reported channel activation by pinacidil and ATP. KATPchannels had a high activity in the control and were blocked by ADP; the subsequent addition of pinacidil did not enhance the open probability of KATP channels. Pinacidil in the presence of a mixture of AMP-PNP and ADP activated KATP channels. Conclusions: The diverse effects of pinacidil are interpreted with a model of the KATPchannel containing a binding site for pinacidil and two sites for nucleotides, one activatory (A) site and one inhibitory (I) site. Occupation of the A site by ATP or ADP activates the channel, while occupation of the I site by ATP, AMP-PNP, ADP closes the channel. Pinacidil activates the channel and displaces blockers from the I site only if the A site is occupied. Cardiovascular Research 1994;28:841-846
Antidiarrhoeal drugs for acute diarrhoea in children.
Authors: W. A. Cutting, K. M. Elliott
Journal: BMJ (1992)

staff training, and an adequate physical environ- ment and is likely to encounter organisational and logistic problems initially.At purchaser level the organisation of funding will need to be considered, along with what further resources will be necessary for assessing and meeting the needs of some of the most vulnerable and
Junctional diversity in signal joints from T cell receptor beta and delta loci via terminal deoxynucleotidyl transferase and exonucleolytic activity.
Authors: S Candéias, K Muegge, S K Durum
Journal: The Journal of Experimental Medicine (1996)

The site-specific V(D)J recombination reaction necessary to assemble the genes coding for immunoglobulin (Ig) and T cell receptor (TCR) variable regions is initiated by a precise double strand cut at the border of the recombination signals flanking the genes. Extensive processing of the coding ends before their ligation accounts for most of the Ig and TCR repertoire diversity. This processing includes both base additions to and loss from the coding ends. On the other hand, it has generally been thought that signal ends are not modified before they are fused, and that signal joints consist of a perfect head-to-head ligation of the recombination signals. In this study, we analyzed signal joints created during the rearrangement of different TCR-beta and TCR-delta genes in thymocytes. We show that a significant fraction (up to 24%) of these signal joints exhibits junctional diversity. This diversity results from N nucleotide additions for TCR-beta signal joints, and from N additions and exonucleolytic digestion for TCR-delta joints. Altogether, our findings suggest that: (a) signal ends can undergo some of the same modifications as coding ends, (b) inversional rearrangement generates more diversity than deletional events, and (c) fine differences exist in the recombinase/DNA complexes formed at each rearranging locus.
Catheter-based intracoronary myocardial adenoviral gene delivery: importance of intraluminal seal and infusion flow rate
Authors: Sitaram M Emani, Ashish S Shah, Michael K Bowman, Sitaramesh Emani, Katrina Wilson, Donald D Glower, Walter J Koch
Journal: Molecular Therapy (2003)

Although percutaneous, adenoviral-mediated intracoronary gene delivery to the heart has been demonstrated in some species, consistent and safe methodology is needed before clinical applicability is possible. In this study, we examine the effects of altering intracoronary flow rate and obtaining an adequate seal between the catheter and the coronary lumen on successful cardiac gene delivery and myocardial injury in both piglets and adult rabbits. To study the efficacy of in vivo myocardial gene transfer, we utilized adenoviral vectors containing either the β2-adrenergic receptor or β-galactosidase. The left circumflex coronary artery of piglets and the right coronary artery of rabbits were catheterized under fluoroscopic guidance and adenovirus solutions were injected using varying flow rates with or without balloon inflation. Successful transgene delivery to the heart was determined ∼1 week after coronary infusions. Histologic analysis was also performed in all animals to determine the extent of myocardial injury. Our results indicate that efficient and reproducible cardiac transgene expression utilizing intracoronary delivery is dependent upon the infusion flow rate and, in larger animals, requires an intraluminal seal. Excessive flow rate is associated with greater myocardial injury. Thus, conditions can be established and controlled to improve future investigational and clinical application of catheter-based intracoronary myocardial gene therapy.
Altered cytokine activities are related to the suppression of synthesis of normal immunoglobulin in multiple myeloma
Authors: Michio Kawano, Koji Iwato, Hideki Asaoku, Osamu Tanabe, Hideo Tanaka, Hideaki Ishikawa, Atsushi Kuramoto
Journal: American Journal of Hematology (1989)

Abstract The content of peripheral blood B cells (B 1 + ) was reduced in patients of multiple myeloma (MM) and not in those with benign monoclonal gammopathy (BMG) compared to normal donors ( P &lt; 0.01). This observation correlated with the suppression of synthesis of normal immunoglobulin (Ig) in MM. Thus, cytokine activities regulating the proliferation of normal mature B cells, such as B cell stimulatory factor 1 (BSF‐1)/ inlerleukin 4 (IL‐4), B cell growth inhibitory factor (BIF) and IL‐2 in peripheral blood T cells, and IL‐1 in peripheral blood adherent cells, were investigated in patients with BMG (n ‐ 7) and MM (n = 28). All patients of MM having a marked suppression of synthesis of all other normal Ig, had significantly lower levels of BSF‐1 activity and inversely higher levels of BIF activity than those of normal donors. However, patients with BMG having no suppression of synthesis of normal Ig had BSF‐1 and BIF activities similar to normal donors. There was no significant difference in IL‐1 and fL‐2 activities between both normal donors and BMG versus MM patients. These data show that in MM altered cytokine activities correlate with suppression of synthesis of normal Ig.
Abstract P1-11-04: A Phase II Preoperative Trial of Concurrent Trastuzumab and Paclitaxel without Anthracycline in HER2-Positive Operable Breast Cancer
Authors: T Sato, T Hayashida, M Takahashi, M Sakata, H Jinno, S Hirose, M Mukai, Y. Kitagawa
Journal: Cancer Research (2010)

Abstract Background Concurrent trastuzumab with paclitaxel/fluorouracil, epirubicin, and cyclophosphamide (P/FEC) chemotherapy as neoadjuvant treatment revealed the high pathologic complete response (pCR) rate of 54.5% (Buzdar, 2007). Deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway either through loss of PTEN or mutation of the catalytic subunit alpha of PI3K (PIK3CA) might confer resistance to trastuzumab. The objective of this study was to determine the efficacy of concurrent administration of trastuzumab and paclitaxel wtihout anthracycline as preoperative chemotherapy. The correlation between deregulation of PI3K and resistance to trastuzumab was also investigated. Patients &amp; methods Patients with HER2-positive, operable breast cancer received 12 cycles of weekly paclitaxel (80 mg/m2) and trastuzumab (4mg/kg loading dose then 2 mg/kg) for 12 weeks before surgery. PTEN status was evaluated by immunohistochemistry. PTEN staining intensity scores was recorded on an integer scale from 0 to 2+ (0; no staining, 1+; reduced staining, and 2+; equal staining as compared to the internal control). Sequencing of PIK3CA exons 9 and 20 was done by PCR amplification and direct sequencing. pCR was defined as no residual invasive carcinoma in the breast. Results Twenty-eight patients were enrolled and assessable for clinical and pathologic responses. The overall response rate was 92.9%, including a complete response in 13 patients and a partial response in 13 patients. The pCR rate was 53.6% (15/28). Twenty-three patients (82.1%) underwent breast concerving surgery. Progesteron receptor (PgR) status was significantly correlated with pCR (p=0.025). Eight of 24 patients (33.3%) were scored PTEN negative. PIK3CA mutations were identified in 4 of 13 patients (30.8%). There was no significant difference in pCR rate and PTEN loss/PIK3CA mutation. Correlation of PgR status and pCR Conclusions These data indicate that the combination of trastuzumab and paclitaxel without anthracycline is effective preoperative chemotherapy with high pCR rate. PTEN loss and/or PIK3CA mutation were not useful predictors of resistance to trastuzumab. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-04.
Immunological profiling of tuberculosis-associated immune reconstitution inflammatory syndrome and non-immune reconstitution inflammatory syndrome death in HIV-infected adults with pulmonary tuberculosis starting antiretroviral therapy: a prospective observational cohort study
Authors: Shruthi Ravimohan, Neo Tamuhla, Andrew P Steenhoff, Rona Letlhogile, Kebatshabile Nfanyana, Scarlett L Bellamy, Rob Roy MacGregor, Robert Gross, Drew Weissman, Gregory P Bisson
Journal: The Lancet Infectious Diseases (2015)
An African's Mental Outlook in Britain
Authors: W. I. B. Onuigbo
Journal: BMJ (1958)

The double blind technique was used throughout with the dose standardized at two tablets three times a day (120 mg.daily).In every case all other psychiatric treatment was withdrawn for the duration of the trial.Substantial improvement was noticed in three patients and some improvement in a further five.No side-effects were noted.It would appear that further trials with this drug in disturbed hallucinated patients would be justified and possibly very helpful.I should like to thank Dr. D. F. Macgregor, medical superin- tendent of Carlton Hayes Hospital, for his co-operation and assistance with the trial.Also Mr. Mills
Eosinophilia during Intensive Gold Therapy
Authors: Edward H. Reisner, Lyon Lapin, Otto Steinbrocker
Journal: New England Journal of Medicine (1949)

IN THE course of a study of intensive chrysotherapy with aurothioglycanilide (lauron) already reported,1 serial hematologic observations revealed a constant and often striking increase in the esoinophil count, which is the subject of this report.Material and MethodsEighteen patients were treated with bi-weekly injections of gold. Sixteen received aurothioglycanilide (lauron), 1 received solganol-B oleosum, and 1 received myochrysine. The total dosage given ranged from 1 gm. to 10 gm in a period of twenty-four to fifty-six days. Prior to every injection of gold, each patient received a complete blood count, platelet count and prothrombin-time determination.ResultsNo toxic reactions . . .
Abstract LB-18: Bcl2-associated athanogene 3 and major vault protein regulate cell survival and resistance to apoptosis in senescent cells by regulating ERK activation
Authors: Martina Pasillas, Sarah Shields, Rebecca Reilly, Laoighse Mulrane, Jan Strnadnel, Karin Jirstrom, Darran O Connor, William Gallagher, Steven Gonias, Judith Coppinger
Journal: Cancer Research (2014)

Abstract Senescence is a prominent solid tumor response to therapy in which cells avoid apoptosis and instead enter into prolonged cell cycle arrest. We applied a quantitative proteomics screen to identify signals that lead to therapy-induced senescence (TIS) and discovered that Bcl2-associated athanogene 3 (Bag3) is upregulated after adriamycin treatment in MCF7 cells. Bag3 protein is a member of the BAG family of co-chaperones that interacts with Hsp70. Bag3 also regulates major signaling pathways. Mass Spectrometry analysis of the Bag3 Complex revealed a novel interaction between Bag3 and Major Vault Protein (MVP). Silencing of Bag3 or MVP shifts the cellular response to adriamycin in favor apoptosis. We demonstrate that Bag3 and MVP contribute to apoptosis resistance in TIS by activation of extracellular signal-regulated kinase1/2 (ERK1/2). Bag3 and MVP were required for ERK1/2 activation in response to adriamycin and silencing either gene product decreased cell survival in response to the drug. An increase in nuclear accumulation of MVP is observed during TIS and the shift in MVP subcellular localization is Bag3-dependent. We propose a model in which Bag3 binds to MVP and facilitates MVP accumulation in the nucleus, which sustains ERK1/2 activation. We demonstrate that Bag3 and MVP are expressed in a panel of diverse breast cancer cell lines and human tumor samples from patients. Silencing of Bag3 and MVP shifts the response to apoptosis and regulates ERK1/2 signaling in ER positive MCF7, ZR751 cell lines and triple negative MDA-MB-231 and MDA-MB-468 cells. Overall this study highlights Bag3-MVP as an important complex that regulates a potent pro-survival signaling pathway in breast cancer. Citation Format: Martina Pasillas, Sarah Shields, Rebecca Reilly, Laoighse Mulrane, Jan Strnadnel, Karin Jirstrom, Darran O Connor, William Gallagher, Steven Gonias, Judith Coppinger. Bcl2-associated athanogene 3 and major vault protein regulate cell survival and resistance to apoptosis in senescent cells by regulating ERK activation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-18. doi:10.1158/1538-7445.AM2014-LB-18
Drug treatment during Ramadan. Don't be complacent about diabetes.
Authors: A E Gold, K M MacLeod, B M Frier
Journal: BMJ (1993)

gram would lead to smaller myocardial infarcts in 476 patients (without cerebral haemorrhage) for every one patient with cerebral haemorrhage with- out myocardial infarction; thrombolysis would be life saving in 19 of these cases.These benefit:risk ratios are even more favourable with thrombolysis before admission to hospital.Two trade offs have to be considered to maximise benefit from thrombolytic treatment: the sensitivity versus the specificity of whatever methods are used for predicting myocardial infarction, and the increasing accuracy of the diagnosis with the time from the onset of symptoms versus the waning efficacy of thrombolysis.The problem is to find the optimal balance between causing disability or death by giving thrombolytic treatment to those without myocardial infarction and causing disability or death by withholding the treatment from those with myocardial infarction.We suggest that use of ST elevation as a precondition for giving thrombolytic treatment errs in the latter direction.
In-vitro synthesis of antibodies to Toxoplasma gondii by lymphocytes from HIV-1-infected patients
Authors: J-P. Vendrell, M-F. Huguet, J. Ngou, C. Michard, A. Serre, J. Reynes, N. Atoui, M. Segondy, F. Pratlong
Journal: The Lancet (1993)
The limits of palliative care
Authors: G. Winyard, L. Macdonald
Journal: BMJ (2014)

Patients wanting the sort of open discussion about their impending death that Boyd and Murray advocate will have one topic denied them; taking their own life should palliative care prove ineffective.1 This option is important because the medical literature demonstrates clearly the limits of even the best palliative care.2 The medical and religious establishments accept this but contend that the suffering of a small number of individuals is a necessary price …
Magnetic Ligation Method for Quantitative Detection of MicroRNAs
Authors: Monty Liong, Hyungsoon Im, Maulik D. Majmudar, Aaron D. Aguirre, Matthew Sebas, Hakho Lee, Ralph Weissleder
Journal: Advanced Healthcare Materials (2014)

A magnetic ligation method is utilized for the detection of microRNAs among a complex biological background without polymerase chain reaction or nucleotide modification. The sandwich probes assay can be adapted to analyze a panel of microRNAs associated with cardiovascular diseases in heart tissue samples.
Adenocarcinoma of the Colon With Hepatic Metastases
Authors: Arnold W. Levine
Journal: JAMA (1982)

IT IS estimated that colorectal cancer will have caused 54,900 deaths in 1981. Hepatic metastases in these patients signal a bleak prognosis, as the average duration of life following this discovery is six to 12 months.<sup>1,2</sup>In a very select group of patients with solitary hepatic lesions, prolonged survival can be obtained by surgical resection.<sup>3</sup>In the patient with unresectable metastases, systemic chemotherapy and radiotherapy provide palliation, but prolonged survival is rare. This report reviews the experience at Milwaukee County General Hospital (MCGH) with intravenous (IV) and oral fluorouracil therapy in patients with hepatic metastasis from colorectal carcinoma and includes a remarkable 14-year, 11-month survivor. <h3>Materials and Methods</h3> Eight hundred seventy-three cases of colorectal cancer were registered with the MCGH tumor registry between 1955 and 1978. This review included patients with resected primary cancers and histologically proved hepatic metastases either at the time of initial laparotomy or later.
Get basics right to improve acute kidney injury, says consensus conference
Authors: B. Christie
Journal: BMJ (2012)

Every hospital in the United Kingdom is being urged to produce fluid therapy guidelines in an attempt to improve the care of acute kidney injury and potentially save thousands of lives a year.

A consensus conference organised by the Royal College of Physicians of Edinburgh also supports the use of electronic alerts to warn clinicians of a patient’s deteriorating condition and calls for better training and education for clinical teams.

Acute kidney injury is a common condition that affects around a fifth of hospital patients in the UK and is associated with poor outcomes. Death rates from the condition have not fallen in the past 40 years, and a National Confidential Enquiry into …