tbuckley/cabot-search huggingface dataset:
Systemic Administration of Platelets Incorporating Inactivated Sendai Virus Eradicates Melanoma in Mice
Authors: Tomoyuki Nishikawa, Li Yu Tung, Yasufumi Kaneda
Journal: Molecular Therapy (2014)

Tumor microenvironments include a number of fibrin clots due to the microbleeding caused by cancer cell invasion into blood vessels, which suggests the potential utility of a platelet vector for systemic cancer treatment. We previously reported that inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ-E) activates anti-tumor immunity and induces cancer cell-selective apoptosis. The hemagglutination activity that blocks the systemic administration of HVJ-E was dramatically attenuated by incorporation into platelets. Platelets incorporating HVJ-E (PH complex) were then injected into the tail veins of B16F10 melanoma-bearing mice. The PH complex primarily accumulated in tumor tissues and caused the significant accumulation of various immune cells in the tumor bed. Injections of the PH complex to the melanoma-bearing mouse significantly reduced the tumor size, and the tumor growth was ultimately arrested. Secretion of the chemokine regulated upon activation normal T-expressed and presumably secreted (RANTES) was upregulated following PH stimulation. The RANTES-depletion in melanoma-bearing mice significantly attenuated the cytotoxic T lymphocyte activity and led to a dramatic abrogation of the mouse melanoma suppression induced by the PH complex. Thus, a platelet vector incorporating viral particles, a Trojan horse for cancer treatment, will provide a new approach for cancer therapy using oncolytic viruses. Tumor microenvironments include a number of fibrin clots due to the microbleeding caused by cancer cell invasion into blood vessels, which suggests the potential utility of a platelet vector for systemic cancer treatment. We previously reported that inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ-E) activates anti-tumor immunity and induces cancer cell-selective apoptosis. The hemagglutination activity that blocks the systemic administration of HVJ-E was dramatically attenuated by incorporation into platelets. Platelets incorporating HVJ-E (PH complex) were then injected into the tail veins of B16F10 melanoma-bearing mice. The PH complex primarily accumulated in tumor tissues and caused the significant accumulation of various immune cells in the tumor bed. Injections of the PH complex to the melanoma-bearing mouse significantly reduced the tumor size, and the tumor growth was ultimately arrested. Secretion of the chemokine regulated upon activation normal T-expressed and presumably secreted (RANTES) was upregulated following PH stimulation. The RANTES-depletion in melanoma-bearing mice significantly attenuated the cytotoxic T lymphocyte activity and led to a dramatic abrogation of the mouse melanoma suppression induced by the PH complex. Thus, a platelet vector incorporating viral particles, a Trojan horse for cancer treatment, will provide a new approach for cancer therapy using oncolytic viruses.
Ventilatory Management of Respiratory Failure in Asthma
Authors: Charles Wiener
Journal: JAMA (1993)

<h3>CASE PRESENTATION</h3> The patient whom I wish to discuss this morning is unable to be present because she is dead. What I want to talk about is why that happened, and how it could possibly have been prevented. She was a 60-year-old nonsmoking woman who had asthma since the age of 16 years. She had been hospitalized seven times for asthma since 1980, but had never been intubated. She had been given prednisone intermittently, but never for more than 3 months at a time. There was no history of cardiac disease. Fourteen days prior to admission, she complained of dyspnea, went to the emergency department (ED), and was given nebulized albuterol, a theophylline drip, and a bolus of methylprednisolone. She was discharged on a 10-day tapering course of prednisone. She came back to the ED 2 days before admission because the dyspnea had recurred. She was given the same medications,
Atlas of External Diseases of the Eye, vol 4: Anterior Chamber, Iris, and Ciliary Body
Authors: Herbert E. Kaufman
Journal: JAMA (1974)

This volume is the fourth in a series of superb teaching atlases on external ocular disease. It continues the extremely high quality of the previous works and, with its unique format, provides a kind of visual teaching experience that cannot be equaled anywhere. The book is more than an atlas. The text consists of typical case histories illustrating the major disease entities that involve the anterior chamber (in part 1), the iris (in part 2), and the ciliary body (in part 3). Although such a presentation cannot encompass the complete course of variations of every single disease, the cases, clearly, are chosen with great care. They are typical, represent almost all the important entities involving these structures, and exemplify what can be expected in the clinical course of these diseases and in the complications that might be anticipated. Since the pictures shown are from the cases documented, the case histories
Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac
Authors: Marianna Max, Y. Gopi Shanker, Liquan Huang, Minqing Rong, Zhan Liu, Fabien Campagne, Harel Weinstein, Sami Damak, Robert F. Margolskee
Journal: Nature Genetics (2001)
Five Futures for Academic Medicine
Authors: Shally Awasthi, Jil Beardmore, Jocalyn Clark, Philip Hadridge, Hardi Madani, Ana Marusic, Gretchen Purcell, Margaret Rhoads, Karen Sliwa-Hähnle, Richard Smith, Tessa Tan-Torres Edejer, Peter Tugwell, Tim Underwood
Journal: PLoS Medicine (2005)

The International Campaign to Revitalise Academic Medicine (ICRAM) considered current global instabilities and future drivers of change, and then created five scenarios of how academic medicine might look in 2025.
Renal Adaptation to Anemia
Authors: ANITA C. APERIA, AVERILL A. LIEBOW, LATHROP E. ROBERTS
Journal: Circulation Research (1968)

Renal adaptation to anemia was studied in dogs that had been bled repeatedly during a week to produce hematocrit values of between 12 and 21%. Total renal blood flow was unaltered despite a significant increase in cardiac output. Total renal oxygen consumption was within normal limits, but the Po 2 of cortical tissue was significantly reduced. Glomerular filtration rate and therefore filtered sodium load were reduced. These alterations were interpreted as resulting from preglomerular vasoconstriction together with a decrease in postglomerular vascular resistance, the latter perhaps a consequence chiefly of the diminished blood viscosity. Sodium reabsorption in relation to filtered sodium load was unimpaired in anemic animals; actually the sodium excretion factor was lower than in normal animals. It is concluded that the maintenance of normal renal function in the anemic animal is obtained by a decrease in work load (i.e. reduced glomerular filtration rate) and more efficient oxygen extraction related to increased blood tissue Po 2 gradient. Increased titers of erythropoiesis-stimulating substance could be demonstrated in these anemic animals. It is suggested that the low cortical tissue Po 2 is responsible for the release of this factor.
Reverse transcriptase activity in human normal and psoriatic skin samples
Authors: J.-P. Molès, A. Tesniere, J.-J. Guilhou
Journal: British Journal of Dermatology (2007)

About half of the human genome is composed of ancient transposable elements that became integrated in the genome throughout the course of evolution by DNA transposition or by retrotransposition. Most of these elements have degenerated. However, a few of them have conserved their coding capacities and could still have a role in physiological and pathological processes. OBJECTIVES To investigate whether reverse transcriptase (RT) of human endogenous retroelements can be expressed at the protein level and can also be functional, and to associate RT expression and activity to a pathological situation, namely psoriasis.Expression of RT proteins was investigated by immunohistochemistry on normal (n = 11), psoriatic (n = 19) and atopic (n = 12) skin sections and by Western blot on normal skin protein extracts. RT activity was measured by a colorimetric method in protein extracts from normal (n = 17) and lesional psoriatic (n = 35) skin. Two assays were performed in each extract: one was optimized for Moloney murine leukaemia virus or mammalian C-type retroviruses, and the other for mouse mammary tumour virus or D-type retroviruses.RT proteins were detected in the uppermost layer of the epidermis and in a few dermal cells of normal skin. The main protein had a molecular weight of 57 kDa. An increased number of RT-positive cells was stained in the psoriatic lesion both within the epidermis and within the dermal compartment. In addition, a massive staining was noted in Munro's abscesses. Finally, RT activities were 2-3 times higher in psoriatic protein extracts than in normal skin protein extracts.Active endogenous retroelements can produce functional RT proteins. In normal skin, we observed RT expression in all samples tested whereas RT activity was barely detectable. In psoriatic samples, the number of RT-positive cells was increased, as was the RT activity. This latter characteristic allowed us to determine a subset of psoriatic samples with an increased Mg(2+) RT activity. These results suggest that a basal level of endogenous retroelement activity exists in normal skin and that keratinocyte hyperproliferation and/or inflammation observed in psoriasis promote this activity. The role of endogenous retroelements in skin physiology and pathology deserves attention.
Hypoxia, Not the Frequency of Sleep Apnea, Induces Acute Hemodynamic Stress in Patients With Chronic Heart Failure
Authors: Joshua D. Gottlieb, Alan R. Schwartz, Joanne Marshall, Pamela Ouyang, Linda Kern, Veena Shetty, Maria Trois, Naresh M. Punjabi, Cynthia Brown, Samer S. Najjar, Stephen S. Gottlieb
Journal: Journal of the American College of Cardiology (2009)
Early treatment with tranexamic acid reduced bleeding death in patients with clinically important hemorrhage due to trauma
Authors: Eddy Lang
Journal: Annals of Internal Medicine (2011)

Source Citation The CRASH-2 collaborators. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011;377:1096-101. 21439633
New political party will target prime minister and five others implicated in NHS changes
Authors: G. Iacobucci
Journal: BMJ (2012)

A new political party formed by doctors opposed to the UK government’s changes to healthcare will aim to unseat the prime minister, David Cameron, the chancellor of the exchequer, George Osborne, and the former health secretary Andrew Lansley at the next election.

The National Health Action (NHA) party, launched with the aim of protecting NHS services that it believed were being threatened by the government’s changes and austerity measures, will also target the current health secretary Jeremy Hunt, the Liberal Democrat minister David Laws, and the junior health minister Dan Poulter, himself a trained doctor.

The identity of those who will challenge incumbent MPs has yet to be determined, as the selection process is still ongoing. But the party has …
An Image of the Medical Profession
Authors: Julian MarDock
Journal: JAMA (1962)

<h3>To the Editor:—</h3> The image of the physician and of the medical profession in general is unfortunately being formed in the mind of the public through the public's contact with these personalities: Your receptionist who informs your patient that the doctor can see no one else today, that he always takes tomorrow off, that he is going to the lake cottage for the week-end, and that he can see the patient on Tuesday. The collection agency who threatens your patient with everything from a court trial to wage attachment so that they might collect their percentage. The clerk in the emergency room who tells the patient to have a seat until called and then calls him 4 hours later. The small-claims court judge who collects your accounts which were referred there without your knowledge. The "administrator" of a proprietary clinic or hospital who must have
69. Tumor-Targeting Innumogene Therapy by Mesenchymal Stem Cells Expressing CX3CL1
Authors: Hong Xin, Masahiko Kanehira, Hiroyuki Mizuguchi, Takao Hayakawa, Toshihiro Nukiwa, Yasuo Saijo
Journal: Molecular Therapy (2005)

Top of pageAbstract
Bone-marrow derived mesenchymal stem cells (MSC) have high proliferative capacity and can differentiate into adipocytes, chondrocytes, osteoblasts, and probably other cells types. Recent studies reported that MSC migrates to the tumor and contributes to the formation of stromal tissue in the solid tumor, suggesting that MSC can be useful for tumor targeting of gene therapy. Since MSC lacks coxsackievirus-adenovirus receptor (CAR), we first investigated the efficiency of infection by either regular Ad vector or Ad-RGD vector, and then investigated anti-tumor effects by MSC expressing CX3CL1 (fractalkine) using Ad-RGD vector expressing CX3CL1 (AdRGDFKN). Murine MSC was infected either AdLacZ or AdRGDLacZ at different doses in vitro, and b-Gal staining positive cells were counted after 48 h infection. MSC infected with AdLacZ demonstrated only 2% positive cells, whereas MSC with AdRGDLacZ demonstrated 18% positive cells at 100 MOI. These results indicated that Ad-RGD could efficiently infect to the MSC. MSC infected with AdRGDFKN in vitro at 100 MOI revealed over 68% MSC expressed CX3CL1 on the cell membrane by FACS analysis. These MSC infected with AdRGDFKN (5|[times]|105/mouse) were injected into subcutaneously transplanted C26 tumor (5|[times]|105/mouse) on day 5. The C26 tumor regressed tumor growth by 59% compared to control tumor on day 22. Intravenous injection of MSC (5|[times]|105/mouse) of GFP mice into mice with established C26 pulmonary metastases led to incorporation of MSC in the tumor architecture. Intravenous injection of MSC-transduced with AdRGDFKN (5|[times]|105/mouse) into mice with established C26 pulmonary metastases suppressed the growth of pulmonary metastases and significantly reduced the number (PBS, 147.2; MSC-RGDLacZ, 136.2; MSC-RGDFKN, 16.3; BALB 3T3-RGDFKN, 157.2) of the metastasis in the C26 model on day 12, and prolonged mouse survival. These results indicate that MSC can be used for tumor-targeting immunogene therapy for multiple metastatic tumors.
Genes Regulated by miRNA in Endocrine-Resistant Breast Tumours.
Authors: A. Larionov, D. Faratian, H. Caldwell, A. Sims, A. Fawkes, L. Murphy, L. Renshaw, J. Dixon, J. Dixon
Journal: Cancer Research (2009)

Abstract RationaleChange in genes expression is one of the major molecular drivers of tumour growth. Mechanisms controlling genes expression include transcriptional factors, mutations, aberrations in gene copy number, epigenetic mechanisms and micro-RNA (miRNA) regulation. The last mechanism has been discovered recently and there is a need to investigate its involvement in genes regulation in endocrine resistant breast tumours.Methods and ResultsTo identify genes regulated by miRNA in endocrine resistant breast tumours we collected frozen biopsies from a series of 51 tumours growing on endocrine treatment (aromatase inhibitors or tamoxifen, post-menopausal patients). Gene expression profiles were obtained using Illumina HT-12 micro-arrays; miRNA expression profiles were obtained using Illumina DASL® Sentrix Array Matrix.Unsupervised hierarchical clustering using 50 most variable miRNAs split tumours into two major clusters (25 and 26 tumours each). We suggest that genes differentially expressed between these two clusters can be potentially regulated by miRNA. The top differentially expressed genes included SAA1, VTCN1, SLC40A1, FBLN1, COL17A1, HDC and CD59.An alternative bioinformatics approach was based on correlations between mRNA and miRNA in the studied tumours. Initially we identified 66 genes negatively correlated with at least one miRNA (r&amp;lt;-0.6). Then we screened the correlated pairs to identify those in which miRNA has target sequence within the corresponding gene. This approach yielded just 2 genes: RAG1 and USP19: RAG1 being potentially regulated by mir92 and USP19 regulated by miR15a.DiscussionEndocrine resistance is a major obstacle in treatment of many breast cancer patients. Molecular mechanisms of the resistance are yet unclear. The abstract presents a sub-group analysis within a larger study, aimed to investigate molecular mechanisms underlying endocrine resistance at both mRNA and miRNA levels. Most of the identified potential miRNA-regulated genes have not been previously reported in the context of breast cancer biology. On our knowledge, this study represents the first systematic attempt to identify genes regulated by miRNA in endocrine-resistant breast cancers. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5149.
Endothelium and NOTCH specify and amplify aorta-gonad-mesonephros–derived hematopoietic stem cells
Authors: Brandon K. Hadland, Barbara Varnum-Finney, Michael G. Poulos, Randall T. Moon, Jason M. Butler, Shahin Rafii, Irwin D. Bernstein
Journal: Journal of Clinical Investigation (2015)

Hematopoietic stem cells (HSCs) first emerge during embryonic development within vessels such as the dorsal aorta of the aorta-gonad-mesonephros (AGM) region, suggesting that signals from the vascular microenvironment are critical for HSC development. Here, we demonstrated that AGM-derived endothelial cells (ECs) engineered to constitutively express AKT (AGM AKT-ECs) can provide an in vitro niche that recapitulates embryonic HSC specification and amplification. Specifically, nonengrafting embryonic precursors, including the VE-cadherin-expressing population that lacks hematopoietic surface markers, cocultured with AGM AKT-ECs specified into long-term, adult-engrafting HSCs, establishing that a vascular niche is sufficient to induce the endothelial-to-HSC transition in vitro. Subsequent to hematopoietic induction, coculture with AGM AKT-ECs also substantially increased the numbers of HSCs derived from VE-cadherin⁺CD45⁺ AGM hematopoietic cells, consistent with a role in supporting further HSC maturation and self-renewal. We also identified conditions that included NOTCH activation with an immobilized NOTCH ligand that were sufficient to amplify AGM-derived HSCs following their specification in the absence of AGM AKT-ECs. Together, these studies begin to define the critical niche components and resident signals required for HSC induction and self-renewal ex vivo, and thus provide insight for development of defined in vitro systems targeted toward HSC generation for therapeutic applications.
Immediate Hemodynamic Response of Patients with Atrioventricular Block and Cardiac Failure to Transvenous Pacing
Authors: FREDARICK L. GOBEL, JOSE R. MEDINA, CLARENCE A. GUENTER, YANG WANG, David P. Olds
Journal: Circulation (1969)

Immediate hemodynamic improvement in patients with complete heart block occurs when the ventricular rate is increased by electrical pacing. During pacing, there is reduction in the pulmonary artery wedge, right atrial, and left and right ventricular filling pressures. The mean rate of ejection, stroke volume, and stroke work decreased following pacing, whereas the ejection time per minute increased, and dye curves assumed a more normal configuration. Very little change was noted in the resting cardiac output. The paced heart is able to obtain greater increases in cardiac output, stroke volume, and mean rate of ejection during exercise than when unpaced. In addition, pacing tends to return elevated exercising filling pressures in the right and left ventricles toward normal.
Negative predictive value of drug skin tests in investigating cutaneous adverse drug reactions
Authors: J. Waton, P. Tréchot, C. Loss-Ayav, J.L. Schmutz, A. Barbaud
Journal: British Journal of Dermatology (2008)

Drug skin tests are useful in aetiological analyses of cutaneous adverse drug reactions to determine if the drug can be rechallenged, or to avoid a cross-reaction with a substitute drug.To evaluate the negative predictive value of drug skin tests.We retrospectively analysed the files of patients referred for drug reactions. We have enrolled those having strictly determined drug reactions with clinical features, delayed onset after drug intake, drug causality assessment, and negative drug skin tests followed by drug administration. Oral provocation tests or substitution tests with a drug of the same class as that suspected of causing the drug reactions were performed.From 1957 files analysed, 200 patients were included. After 403 patch tests, 403 prick tests and 304 intradermal tests, which were all negative, 260 oral provocation tests and 143 substitution tests were done; 307 different drugs were rechallenged. There were 42 positive drug re-administrations in 27 oral provocation tests and 15 substitution tests. The negative predictive value of our drug skin tests was 89.6%. The negative predictive value for beta-lactams was 87% for oral provocation tests and 96% for substitution tests, and for corticosteroids it was 100% and 74%, respectively.Negative drug skin tests do not eliminate the responsibility of a drug in drug reactions, and must be followed by drug re-administration under hospital surveillance.
Conflicts of interest are common at FDA
Authors: Jeanne Lenzer
Journal: BMJ (2006)

Members of drug advisory committees at the US Food and Drug Administration often have financial conflicts of interest and those conflicts affect voting patterns, says a study in JAMA (2006;295: 1921).

In 73% of the 221 meetings analysed, at least one advisory member or consultant had one or more conflicts. On an individual level, 28% of advisory members and voting consultants had conflicts. The researchers found that if panellists with conflicts had been excluded, voting margins for the index drug would have been less favourable. In none of the instances studied would exclusions have changed the majority vote for or against approval.

The study, by …