tbuckley/cabot-search huggingface dataset:
Blockade of Treg derived TGF-β abrogates suppression of effector T cell function within the tumor microenvironment
Authors: Sadna Budhu, David Schaer, Yongbiao Li, Alan Houghton, Samuel Silverstein, Taha Merghoub, Jedd Wolchok
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Regulatory T cells (Treg) play a role in suppression of anti-melanoma immunity; however, the exact mechanism is poorly understood. Through intravital two photon microscopy, we found that Pmel-1 effectors engage in cell-cell interactions with tumor resident Tregs. To determine if
CHARACTERISTICS AND OUTCOMES OF PATIENTS WITH ATRIAL FIBRILLATION AND SIGNIFICANT VALVULAR LESIONS: EXPERIENCE FROM THE ROCKET AF TRIAL
Authors: Guenter Breithardt, Helmut Baumgartner, Scott Berkowitz, Anne Hellkamp, Jonathan Piccini, Susanna Stevens, Yuliya Lokhnygina, Manesh Patel, Jonathan Halperin, Daniel Singer, Graeme Hankey, Werner Hacke, Richard Becker, Christopher Nessel, Kenneth Mahaffey, Keith Fox, Robert Califf
Journal: Journal of the American College of Cardiology (2013)
Isolated testicular relapse in boys with acute lymphoblastic leukaemia: treatment and outcome.
Authors: J Tiedemann, J M Chessells, R M Sandland
Journal: BMJ (1982)

In 22 boys among a group of 169 with acute lymphoblastic leukaemia the first relapse occurred in the testis. In 14 of these late isolated testicular relapse was detected on routine biopsy or became apparent after treatment was electively stopped. Eleven of these boys were treated with reinduction, irradiation of 2400 rads to both testicles, intrathecal methotrexate, and two years of chemotherapy; 10 remained well and were in second complete remission from two and a half to five and a half years later. It is concluded that boys with late isolated testicular relapse fare better than those with late marrow relapse and may have a change of long-term disease-free survival.
Thalidomide Back—Under Strict Control
Authors: Charles Marwick
Journal: JAMA (1997)

THALIDOMIDE, the notoriously teratogenic agent of the 1960s, is about to become a prescribed drug. Just 17 days after an advisory committee of the Food and Drug Administration (FDA) recommended that the acting commissioner give marketing approval to thalidomide for treatment of erythema nodosum leprosum (ENL), a complication of lepromatous leprosy, FDA informed the maker that the drug would be approved. This use has been studied since 1965. The condition is estimated to affect only a few thousand people in the United States, but when approval is granted, the door will be open for physicians to prescribe the drug as they wish. A number of uses of thalidomide are under active investigation and some have shown considerable promise. However, even apart from its teratogenic potential, the drug is not without such occasional serious adverse effects—especially with long-term use-—as irreversible peripheral neuropathy. Thalidomide is an inhibitor of the cytokine tumor
THE ULTRACENTRIFUGE AS AN AID IN THE DETECTION OF POLIOMYELITIS VIRUS
Authors: Joseph L. Melnick
Journal: The Journal of Experimental Medicine (1943)

1. By means of differential ultracentrifugation, a purified and concentrated macromolecular fraction has been regularly obtained from infected human, monkey, and chimpanzee stools. This fraction was isolated from sixteen stools in which virus was thought to be present, and inoculated intracerebrally into sixteen monkeys, of which fifteen developed poliomyelitis. 2. Eleven stool specimens in which virus was suspected, when tested separately in eleven monkeys by the intra-abdominal-intranasal method, produced poliomyelitis in two of these animals. When the same specimens were tested separately by the ultracentrifugal-intracerebral method, poliomyelitis developed in ten monkeys out of eleven inoculated. 3. With the intra-abdominal-intranasal method, it has been customary to inoculate the virus present in 1.6 gm. of stool. With the ultracentrifugal-intracerebral method, the virus present in as much as 30 gm. of stool has been inoculated. 4. From one titration experiment it would appear that the ultracentrifugal-intracerebral method is at least 100 times more sensitive than the intra-abdominal-intranasal method.
Abstract 2113: Arsenic hexoxide inhibits NF-κB activity through, at least in part, suppression of IκBα phosphorylation in MCF-7 human breast cancer cells.
Authors: Won Sup Lee, Min Jeong Kim, Ji-Hyun Jung, Jeong Won Yun, Jing Nan Lu, Sang mi Yi, Hye Jung Kim, Seong-Hwan Chang, GonSup Kim, Soon Chan Hong, Woo song Hwa
Journal: Cancer Research (2013)

Abstract Arsenic hexoxide (As4O6) has been used in Korean folk remedy for the treatment of cancer since the late 1980’s. Evidence suggests that the anti-cancer effects of As4O6 are different from those of As2O3. Nuclear factor-κB (NF-κB) is a well-known transcription factor involved in cell proliferation, invasion and metastasis. Here, we investigated the effects of As4O6 on NF-κB activity, NF-κB-regulated gene expressions, and NF-κB-mediated cellular responses. As4O6 suppressed NF-κB activation induced by TNF-α, and the some of the downstream NF-κB-regulated proteins involved in caner proliferation, metastasis and anti-apoptosis. As4O6 also suppressed IκB phosphorylation in a time-dependent manner, suggesting the suppression of NF-κB results from at least in part by inhibiting IκB degradation. We also confirmed the anti-NF-κB activity of As4O6 with synergism with TNF-α at the molecular levels. This study demonstrates that As4O6 inhibits NF-κB activation and NF-κB regulated proteins at least in part through the inhibition of IκB phosphorylation. [This study was supported by a grant from the National R&amp;D Program for Cancer Control, Ministry for Health, Welfare &amp; Family Affairs, Republic of Korea. (0820050), and National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (20120002631).] Keywords: Arsenic hexoxide, Nuclear factor-κB, IκB, cancer Citation Format: Won Sup Lee, Min Jeong Kim, Ji-Hyun Jung, Jeong Won Yun, Jing Nan Lu, Sang mi Yi, Hye Jung Kim, Seong-Hwan Chang, GonSup Kim, Soon Chan Hong, Woo song Hwa. Arsenic hexoxide inhibits NF-κB activity through, at least in part, suppression of IκBα phosphorylation in MCF-7 human breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2113. doi:10.1158/1538-7445.AM2013-2113
PTPL1/PTPN13 Regulates Breast Cancer Cell Aggressiveness through Direct Inactivation of Src Kinase
Authors: Murielle Glondu-Lassis, Mathilde Dromard, Magali Lacroix-Triki, Philippe Nirdé, Carole Puech, Dora Knani, Dany Chalbos, Gilles Freiss
Journal: Cancer Research (2010)

The protein tyrosine phosphatase PTPL1/PTPN13, the activity of which is decreased through allelic loss, promoter methylation, or somatic mutations in some tumors, has been proposed as a tumor suppressor gene. Moreover, our recent clinical study identified PTPL1 expression level as an independent prognostic indicator of a favorable outcome for patients with breast cancer. However, how PTPL1 can affect tumor aggressiveness has not been characterized. Here, we first show that PTPL1 expression, assessed by immunohistochemistry, is decreased in breast cancer and metastasis specimens compared with nonmalignant tissues. Second, to evaluate whether PTPL1 plays a critical role in breast cancer progression, RNA interference experiments were performed in poorly tumorigenic MCF-7 breast cancer cells. PTPL1 inhibition drastically increased tumor growth in athymic mice and also enhanced several parameters associated with tumor progression, including cell proliferation on extracellular matrix components and cell invasion. Furthermore, the inhibition of Src kinase expression drastically blocked the effects of PTPL1 silencing on cell growth. In PTPL1 knockdown cells, the phosphorylation of Src on tyrosine 419 is increased, leading to the activation of its downstream substrates Fak and p130cas. Finally, substrate-trapping experiments revealed that Src tyrosine 419 is a direct target of the phosphatase. Thus, by identification of PTPL1 as the first phosphatase able to inhibit Src through direct dephosphorylation in intact cells, we presently describe a new mechanism by which PTPL1 inhibits breast tumor aggressiveness.
The Use of Heparin
Authors: Daniel Deykin
Journal: New England Journal of Medicine (1969)

ALTHOUGH heparin is a widely accepted drug, there remains much confusion over its mode of action and over preferred routes of administration, dosage and regulation of therapy.Heparin, a potent organic acid, is a mixture of sulfate-containing mucopolysaccharides, with molecular weights ranging between 8000 and 15,000. Because of its strong electrostatic charge, heparin combines with a wide variety of proteins. Its anticoagulant action is a direct result of this property. It prevents the activation of clotting factor IX (PTC or Christmas factor), an essential component of the intrinsic coagulation mechanism. Furthermore, in conjunction with a plasma cofactor, it inhibits the . . .
STUDIES ON THE CONTROL OF ANTIBODY SYNTHESIS
Authors: Neil I. Brody, J. Geoffrey Walker, Gregory W. Siskind
Journal: The Journal of Experimental Medicine (1967)

In the system studied, antigenic competition between two haptenic determinants was found to be of the same extent whether the haptens were on the same or on separate carrier molecules. Suppression of antibody formation to one determinant by administration of passive antibody partially eliminated the depressive effects of antigenic competition when the two haptens were located on separate carrier molecules but had no effect on antibody production to the second hapten when the two determinants were present on the same molecule. The results are discussed in terms of the mechanisms of suppression, antigenic competition, and control of antibody formation.
TUMOUR NECROSIS FACTOR AS AN AUTOCRINE TUMOUR GROWTH FACTOR FOR CHRONIC B-CELL MALIGNANCIES
Authors: F.T. Cordingley, A.V. Hoffbrand, H.E. Heslop, M. Turner, A. Bianchi, J.E. Reittie, A. Vyakarnam, A. Meager, M.K. Brenner
Journal: The Lancet (1988)
Chickenpox with Pneumonia and Pericarditis
Authors: Robert B. Helmly, John O. Smith, Bruno Eisen
Journal: JAMA (1963)

PERICARDITIS is a rare complication of chickenpox and has been reported only once previously. The following is an additional report. <h3>Report of a Case</h3> A 25-year-old white male experienced headache, malaise, and backache on April 23, 1961. The following day he noted sore throat, marked anorexia, a vesicular rash on the face and trunk, and a temperature of 104 F (40 C). The skin lesions became more numerous, spread to the extremities, and eventually evolved through the typical stages of chickenpox. On the third day of illness vomiting occurred and the patient was given penicillin intramuscularly by his private physician. Because of continued severe headache, malaise, anorexia, and fever, he reported to this hospital on the fourth day of his illness. He denied cough and chest pain prior to admission. He had never had chickenpox. He appeared quite ill; his temperature was 104 F, pulse 100 beats per minute and
Thermosensitive Hydrogel PEG–PLGA–PEG Enhances Engraftment of Muscle-derived Stem Cells and Promotes Healing in Diabetic Wound
Authors: Pui Yan Lee, Erin Cobain, Johnny Huard, Leaf Huang
Journal: Molecular Therapy (2007)

Regenerating new tissue using cell transplantation has relied on successful cell engraftment in the host; however, cell engraftment into the diabetic skin wound is not as successful as in many other tissues. We used a biodegradable and biocompatible triblock co-polymer poly(ethylene glycol-b-[dl-lactic acid-co-glycolic acid]-b-ethylene glycol) (PEG–PLGA–PEG), which forms a thermosensitive hydrogel, as a wound dressing and scaffold. We found that the thermosensitive hydrogel increased the engraftment of muscle-derived stem cells (MDSCs) by 20- to 30-fold until day 20, when the wound was completely closed in a db/db genetically diabetic mouse model. At day 9, 30% of the transplanted MDSCs were found to remain, and 15% remained at day 20 after transplantation. The increased engraftment resulted in enhanced wound healing, as indicated by the wound closure rate, epithelium migration, and collagen deposition. Using MDSCs stably expressing β-gal and immunofluorescence, we found that 25% of MDSCs differentiated into fibroblasts, 10% into myofibroblasts, and 10% into endothelial cells. We conclude that using the thermosensitive hydrogel as a scaffold increased the engraftment of MDSCs, which leads to improved diabetic wound healing, possibly by retaining the cells at the wound site for longer. Regenerating new tissue using cell transplantation has relied on successful cell engraftment in the host; however, cell engraftment into the diabetic skin wound is not as successful as in many other tissues. We used a biodegradable and biocompatible triblock co-polymer poly(ethylene glycol-b-[dl-lactic acid-co-glycolic acid]-b-ethylene glycol) (PEG–PLGA–PEG), which forms a thermosensitive hydrogel, as a wound dressing and scaffold. We found that the thermosensitive hydrogel increased the engraftment of muscle-derived stem cells (MDSCs) by 20- to 30-fold until day 20, when the wound was completely closed in a db/db genetically diabetic mouse model. At day 9, 30% of the transplanted MDSCs were found to remain, and 15% remained at day 20 after transplantation. The increased engraftment resulted in enhanced wound healing, as indicated by the wound closure rate, epithelium migration, and collagen deposition. Using MDSCs stably expressing β-gal and immunofluorescence, we found that 25% of MDSCs differentiated into fibroblasts, 10% into myofibroblasts, and 10% into endothelial cells. We conclude that using the thermosensitive hydrogel as a scaffold increased the engraftment of MDSCs, which leads to improved diabetic wound healing, possibly by retaining the cells at the wound site for longer.
Six Area, Six Sign Atopic Dermatitis (SASSAD) severity score: a simple system for monitoring disease activity in atopic dermatitis*
Authors: J. BERTH-JONES
Journal: British Journal of Dermatology (1996)

The Six Area, Six Sign Atopic Dermatitis severity score has proved to be a simple and effective system for recording and monitoring disease activity in atopic dermatitis. The score is obtained by grading six signs (erythema, exudation, excoriation, dryness, cracking and lichenification), each on a scale of () (absent), 1 (mild), 2 (moderate), or 3 (severe), at each of six sites; arms, hands, legs, feet, head and neck, trunk. The maximum score is 108.
Antipyrine clearance (one sample method) in chronic compensated liver diseases (CCLD): A cross-sectional evaluation
Authors: F. Tiné, P. Almasio, G. D'Amico, G. Fiorentino, A. Luca, L. Pasta, F. Politi, D. Rende, L. Pagliaro
Journal: Journal of Hepatology (1989)
Activating STAT6 mutations in follicular lymphoma
Authors: Mehmet Yildiz, Hongxiu Li, Denzil Bernard, Nisar A. Amin, Peter Ouillette, Siân Jones, Kamlai Saiya-Cork, Brian Parkin, Kathryn Jacobi, Kerby Shedden, Shaomeng Wang, Alfred E. Chang, Mark S. Kaminski, Sami N. Malek
Journal: Blood (2014)
Long-Term Follow-up of Renal Function and Histology After Acute Tubular Necrosis
Authors: DONALD T. LEWERS
Journal: Annals of Internal Medicine (1970)

Renal function and histology were evaluated in 30 patients surviving acute tubular necrosis who were followed from 2 to 15 years. Clinical recovery was complete in all patients. Endogenous creatinine clearance was abnormal in 37%, whereas 47% failed to concentrate their urine to an osmotic urine to plasma ratio of 3.0. Two patients have an unexplained progressive deterioration in glomerular filtration rate. Ischemic acute tubular necrosis was followed by an abnormal creatinine clearance in 44% compared with 25% of those with a toxic cause. Toxic acute tubular necrosis was followed by a concentrating defect in 58% compared with 39% of the ischemic group. Phenolsulfonphthalein, intravenous pyelogram, maximal acid excretion, urinalysis, and urine cultures were abnormal in fewer patients. Renal histological changes were minimal and nonspecific. Patients recovering from acute tubular necrosis are clinically normal, and most have normal renal histology. Renal function will approach but not always achieve normal levels in the majority. Progressive deterioration of renal function may occasionally occur.
Colonoscopy in management of colonic strictures.
Authors: R H Hunt, R H Teague, E T Swarbrick, C B Williams
Journal: BMJ (1975)

A total of 160 strictures were examined in 154 patients with the fibreoptic colonoscope. When it was possible to make a pre-examination diagnosis colonoscopy proved it wrong in 52% of cases. Unnecessary laparotomy was probably avoided in over half this series. All strictures of the large bowel should be examined colonoscopially whenever possible before considering surgery.
Hyperphosphorylated paratarg-7: a new molecularly defined risk factor for monoclonal gammopathy of undetermined significance of the IgM type and Waldenström macroglobulinemia
Authors: Sandra Grass, Klaus-Dieter Preuss, Alexandra Wikowicz, Evangelos Terpos, Marita Ziepert, Diana Nikolaus, Yin Yang, Natalie Fadle, Evi Regitz, Meletios A. Dimopoulos, Steven P. Treon, Zachary R. Hunter, Michael Pfreundschuh
Journal: Blood (2011)
If doctors can train part time, why not medical students?
Authors: P. W. Raven
Journal: BMJ (2014)

Part time degrees may better suit some of today’s medical undergraduates for several reasons, writes Peter W Raven , including finances and caring responsibilities

It is increasingly the case that changes in postgraduate medical training are drivers for change in the undergraduate curriculum.1 The shift in postgraduate medical training that followed the UK General Medical Council’s endorsement of less than full time (LTFT) training in October 2012 has yet to generate a response from medical schools.2 We have positively embraced the concept of part time training of junior doctors and yet the only way to study medicine is on a full time course. So should we be offering part time undergraduate courses in medicine?

Undergraduate medicine is a highly regulated programme of study but the GMC does not take a formal position on part time bachelor of medicine, bachelor of surgery (MBBS) degrees. It certainly has no rules against them: as long as students complete their 5500 hours of theoretical and practical training, an MBBS programme can be as short as a four year graduate entry programme or as long as the eight to 10 year MBPhD.

Universities are increasingly well equipped to deliver …
Mapping the Human Genome
Authors: Arthur W. Nienhuis
Journal: New England Journal of Medicine (1978)

The science of genetics has evolved dramatically since Mendel deduced several important principles of inheritance by observing the color of pea seeds. From the visual observation of phenotypic characteristics, steady progress has taken us ever closer to the molecular basis for gene expression — the DNA sequences of individual cells. For several years, molecular geneticists were preoccupied with the biochemical characterization of mutant enzymes and other cell products; recently, more attention has been directed to the study of nucleic acid molecules containing particular gene or messenger RNA (mRNA) sequences. In this issue of the Journal, Orkin and his co-workers show . . .
A Cohort Study of Cyclin D1 Expression and Prognosis in 602 Colon Cancer Cases
Authors: Shuji Ogino, Katsuhiko Nosho, Natsumi Irahara, Shoko Kure, Kaori Shima, Yoshifumi Baba, Saori Toyoda, Li Chen, Edward L. Giovannucci, Jeffrey A. Meyerhardt, Charles S. Fuchs
Journal: Clinical Cancer Research (2009)

Cyclin D1 and cyclin-dependent kinases (CDK) are commonly activated in colorectal cancer. The activity of cyclin D1 can be blocked by CDK inhibitors, including p27 (CDKN1B) and p21 (CDKN1A, which is induced by p53). However, prognostic significance of tumoral cyclin D1 remains uncertain, and no previous study has considered potential confounding effect of p53, p21, p27, and related molecular events [microsatellite instability (MSI), CpG island methylator phenotype, and LINE-1 hypomethylation].Among 602 colon cancer patients (stage I-IV) in two prospective cohort studies, cyclin D1 overexpression was detected in 330 (55%) tumors by immunohistochemistry. Cox proportional hazard models computed hazard ratios (HR) of colon cancer-specific and overall mortalities, adjusted for patient characteristics and tumoral molecular features, including p53, p21, p27, cyclooxygenase-2, fatty acid synthase, LINE-1 methylation, CpG island methylator phenotype, MSI, BMI, KRAS, and BRAF.Cyclin D1 overexpression was associated with a low cancer-specific mortality in Kaplan-Meier analysis (P = 0.006), and in both univariate Cox regression [unadjusted HR, 0.64; 95% confidence interval (CI), 0.47-0.88; P = 0.0063] and multivariate analyses (adjusted HR, 0.57; 95% CI, 0.39-0.84; P = 0.0048). Similar findings were observed for an overall mortality (adjusted HR, 0.74; 95% CI, 0.57-0.98; P = 0.036). Notably, the effect of cyclin D1 on survival might differ by MSI status (P(interaction) = 0.008). Compared with tumors that were both cyclin D1-negative and MSI-low/microsatellite stable, the presence of either cyclin D1 or MSI-high or both seemed to confer better clinical outcome (adjusted HR point estimates, 0.10-0.65).Cyclin D1 overexpression is associated with longer survival in colon cancer.
A PRELIMINARY INVESTIGATION OF THE THEORY OF THE INOCULATION OF MALARIAL FEVER THROUGH THE AGENCY OF MOSQUITOES.
Authors: ALBERT WOLDERT
Journal: JAMA (1900)

For some time past I have been studying the different species of mosquitoes collected in eastern and central Texas, eastern Pennsylvania, and the eastern coast of New Jersey. I learned that during the month of October the<i>Culex pungens</i>was the most common species which prevailed to the greatest extent in all of them. I have made sections of many of them and examined these microscopically. Probably 2000 sections have been made. The subject of entomology is a very important one in connection with this work, and in this department of science there is much room for improvement, such as the classification of mosquitoes. <h3>NATURAL ORDER OF THE MOSQUITO.</h3> The mosquito belongs to the natural order<i>Diptera</i>, sub-order<i>Nemocera</i>, and to the family<i>Culicidæ</i>. Two genera are most commonly known, namely,<i>Culex</i>and<i>Anopheles</i>. The word "mosquito" is derived from the Spanish and Portuguese<i>mosca</i>or the Latin<i>musca</i>, which
Calcium antagonist withdrawal syndrome: objective demonstration with frequency-modulated ambulatory ST-segment monitoring.
Authors: V B Subramanian, M J Bowles, N S Khurmi, A B Davies, M J O'Hara, E B Raftery
Journal: BMJ (1983)

Development of incisional herniaYear 1 Year 3 Year 5 No of patients followed up 564 482 431 No of new hernias 28 14 6factor for which there was a significant difference between patients who had developed a hernia by one year (750" wound infection) and those who developed one subsequently (38O% wound infection) (p < 0 05).Factors that showed no significant difference between the two groups were sex, obesity, malnutrition, malignant disease, coexisting medical conditions, type of incision, postoperative chest infection, and suture materials used.Preliminary data from the follow up after seven years showed that a new hernia had developed in a further four patients out of the 376 patients studied.