tbuckley/cabot-search huggingface dataset:
Pneumococcal-vaccine-induced thrombocytopenia
Authors: M. L. Citron
Journal: JAMA (1982)

To the Editor.—  Pneumococcal vaccine has been used to protect high-risk individuals from pneumococcal infection.1Both local and systemic adverse reactions have been described with the administration of this vaccine.2Kelton3described two patients with immune thrombocytopenia (ITP) who had relapses of their disease after receiving pneumococcal vaccine. This is another case report of the occurrence of thrombocytopenia in a patient with ITP after receiving this vaccine.  Report of a Case.—  A 17-year-old boy had a platelet count of 18,000/μL of two years' duration. A bone marrow examination disclosed increased megakaryocytes, and secondary causes of thrombocytopenia were excluded. A test for platelet-associated IgG was positive. A regimen of 60 mg/day of prednisone was begun. After an initial favorable response to prednisone administration, the platelet count fell to 40,000/μL. A splenectomy was performed five weeks after the initiation of prednisone therapy. On the day of splenectomy, the platelet
86. Transcriptional Gene Silencing in Human Cells
Authors: Zhaoxia Chen, Ali Ehsani, Riggs Art, Rossi J. John, Kevin V. Morris
Journal: Molecular Therapy (2005)

In mammalian cells, small interfering RNA (siRNA) is known to produce post-transcriptional gene silencing (PTGS) in the cytoplasm. We recently reported transcriptional gene silencing (TGS) mediated by siRNAs when targeted to the EF1alpha promoter and delivered to the nucleus of human cells 1. We have expanded our initial observation to address the mechanism of siRNA mediated TGS. We screened the binding potential of DNMT1, 3A, 3A2, 3B1, 3B2, and HP1-alpha, beta, and gamma to the EF52 siRNA. Interestingly, DNMT3A, 3A2, and 3B2 bound EF52 with DNMT3A displaying the most robust binding. Moreover, the observed binding appears to be strand-specific. These data suggest a link between siRNA mediated targeting of genomic regions (promoters), DNA methylation, and chromatin remodeling complexes in mammalian cells. One possible model is that the siRNA binds DNMT3A and specifically targets the promoter. Once targeted to the promoter DNMT3A could then have a secondary interaction with histone deacetylase and/or the histone methyltransferase SUV39H1 2. These interactions would then be expected to ultimately result in histone 3 lysine 9 methylation, gene silencing, and eventually if reinforced, DNA methylation of the targeted promoter.
Abstract 1352: Mechanism of action of AL622, a molecule rationally designed to release an EGFR and a Src kinase inhibitor
Authors: Na Ning, Anne-Laure Larroque-Lombard, Ying Huang, Suman Rao, Bertrand J. Jean-Claude
Journal: Cancer Research (2011)

Abstract In many solid tumors, including prostate and breast carcinomas, it has now been shown that Src synergizes with EGFR to promote cell proliferation and invasion. While molecules with EGFR and Src targeting functions have been designed, prodrugs capable of releasing optimized inhibitors of the two targets are scant. We designed AL622, which contains a quinazoline head targeted to EGFR and a hydrolysable linker that connects it to the PP2-like structure. HPLC analysis showed that this molecule is capable of releasing an EGFR inhibitor and intact PP2 inside the cells. The growth inhibition of AL622 in a panel of isogenic NIH3T3 cell lines (wt, Neu/ErbB2 and Her14/EGFR transfected) in comparison with Gefitinib (a clinically approved strong EGFR inhibitor) and PP2 (a Src-inhibitor) was assessed using the SRB assay. Like Gefitinib, AL622 blocked the proliferation of NIH3T3 cells transfected with the EGFR or Her2 gene. Although Gefitinib was twice as potent, AL622 showed a higher selectivity (fold selectivity = 1.77 for Neu-transfected and 1.63 for HER14-transfected cells). On the other hand, AL622 showed a 5-fold greater potency than PP2 in the EGFR and Her2 transfected cells. It was also much more selective than PP2 (fold selectivity = 35.9 for Neu-transfected and 37.8 for HER14-transfected cells). Western blot analysis in MDA-MB231 cells known to be characterized by Src-EGFR interaction showed that AL622 was capable of inducing a dose-dependent inhibition of EGFR and Src. In contrast, PP2 at an equidose was incapable of blocking EGFR but induced potent Src-inhibition. While Gefitinib induced some Src inhibition, it was less potent than AL622. Results from the wound healing assay showed that AL622 was capable of blocking the motility of 4T1 mouse breast cancer cells at doses comparable with those of PP2. However, a Boyden Chamber invasion assay showed that AL622 was capable of inducing more significant inhibition of invasion when compared with PP2 or the combination of PP2 and Gefitinib. The results in toto suggest that designing molecules to inhibit Src and EGFR can be an effective strategy to block aggressive proliferation and invasion in tumor cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1352. doi:10.1158/1538-7445.AM2011-1352
Bimodal distribution of genomic MLL breakpoints in infant acute lymphoblastic leukemia treatment
Authors: R Jung, U Jacobs, M Krumbholz, T Langer, T Keller, P De Lorenzo, M G Valsecchi, V H J van der Velden, A Moericke, M Stanulla, A Teigler-Schlegel, E R Panzer-Gruemayer, J J M van Dongen, M Schrappe, M L den Boer, R Pieters, W Rascher, M Metzler
Journal: Leukemia (2010)
Peer review will become “the job of the many, not the select few”
Authors: Robert Short
Journal: BMJ (2007)

Organisations that fund research are increasingly asking authors to place their research in open access repositories within a set period of their papers being accepted for publication in peer reviewed journals.

Although the number of bodies introducing such a requirement grew particularly rapidly in 2006, the momentum continues this year, Richard Smith, a board member of the Public Library of Science (PLoS) and former editor of the BMJ , told the BioMed Central colloquium on open access in London last week.

Dr Smith cited a recent article showing that in the first month of 2007 four organisations adopted an open access requirement and five made pledges to adopt such a requirement, while in another five cases there were significant calls for such mandates …
Children born as a result of incest.
Authors: M Super
Journal: BMJ (1981)

were born to Avon residents; 28 (40%) received intensive care and 19 survived (27% of total and 68% of those treated).Follow-up progress is most encouraging so far.There were no survivors among the 44 infants who did not receive respiratory support and parenteral nutrition.The impact of improved newborn care on the survival of low-birthweight infants in England and Wales has also been well demonstrated by Pharoah and Alberman.
354 AE2A,B DEFICIENCY MAY LEAD TO VESICULAR TRAFFICKING ALTERATIONS IN MOUSE CHOLANGIOCYTES
Authors: M. Sánchez de Viteri, E. Sáez, J.T. Salas, R.P.J. Oude Elferink, J. Prieto, J.F. Medina, J.M. Banales
Journal: Journal of Hepatology (2012)
Posttransplant Lymphoproliferative Disease in a Pediatric Patient as Seen on PET/CT Scan
Authors: Sanjeev Bagga
Journal: Clinical Nuclear Medicine (2007)

We present a case of an 18-year-old who had received a renal transplant 4 years ago. He underwent an ultrasound due to pain and fullness in right flank that showed hydronephrosis of the transplant kidney. A percutaneous nephrostomy was performed for hydronephrosis of the transplant kidney because of a new mass in the pelvis as seen on CT scan. This mass was F-18 FDG avid on a PET scan. A biopsy confirmed the diagnosis of posttransplant lymphoproliferative disease. The patient responded to treatment. A follow-up PET scan showed resolution of this mass. PET proved helpful in making the diagnosis and follow-up of the patient.
How to Interpret Investigations Used in Clinical Endocrinology
Authors: Frances K. Widmann
Journal: JAMA (1965)

to Interpret Renal Function Tests.  By Jean F. Porge. Translated by Peter Holmes. 67 pp, with illus. Paper. $3. Williams & Wilkins Co., 428 E Preston St, Baltimore 21202, 1965  These two pocket-sized manuals represent British translations of French monographs. They are part of a series entitled How To Interpret, an ambitious project intended to encapsulate useful material for specific fields of medical interest.    To Interpret Investigations Used in Clinical Endocrinology describes succinctly the significance and pitfalls of many procedures. Some are familiar favorites; others, with a somewhat exotic flavor, will be of largely theoretical interest. The authors, describing a variety of tests for each endocrine gland, bring together in readable form material that frequently is widely dispersed and difficult for the general readerto assemble rapidly. The presentations are clear and brief, resulting in the sacrifice of a few physiological subtleties. Most readers, however, will rejoice in the
Management and referral for trigger finger/thumb
Authors: Sohail Akhtar, Mary J Bradley, David N Quinton, Frank D Burke
Journal: BMJ (2005)

Trigger finger is a common cause of pain and disability in the hand.It is also the fourth most common reason for referral to the hand outpatient clinic and accounts for 1 in 18 of all referrals to our unit.The condition is, however, not solely managed by hand surgeons as it is often treated in the community and by specialist practitioners such as rheumatologists and endocrinologists who encounter it as a secondary manifestation of a primary systemic disorder.From a review of the literature we highlight the presentation of trigger finger, describe the processes involved in developing the condition, and rationalise the treatment options available.We have suggested guidelines and key points of note to aid practitioners in the management and referral of trigger finger and thumb in adults. Sources and search criteriaWe searched Medline and PubMed for relevant English language literature.We used the search terms "trigger finger" and "stenosing tenosynovitis."We identified additional literature from the references of these papers. Presentation and progressionTrigger finger presents with discomfort in the palm during movement of the involved digits.Gradually, or in some cases acutely, the flexor tendon causes a painful click as the patient flexes and extends the digit.The patient may present with a digit locked in a particular position, usually in flexion, which may need gentle passive manipulation into full extension.Spontaneous resolution of symptoms can occur in patients with trigger thumb.w1 EpidemiologyThe condition has a reported incidence of 28 cases per 100 000 population per year, or a lifetime risk of 2.6% in the general population. 1 This rises to 10% in patients with diabetes.Two peaks in incidence occur-the first under the age of eight and the second (more common) in the fifth and sixth decades of life.This bimodal distribution represents two different clinical groups, not only for age but also in incidence, sex distribution, digit affected, treatment, and outcome (table).
CARM1 Is an Important Determinant of ERα-Dependent Breast Cancer Cell Differentiation and Proliferation in Breast Cancer Cells
Authors: Mariam Al-Dhaheri, Jiacai Wu, Georgios P. Skliris, Jun Li, Ken Higashimato, Yidan Wang, Kevin P. White, Paul Lambert, Yuerong Zhu, Leigh Murphy, Wei Xu
Journal: Cancer Research (2011)

Breast cancers with estrogen receptor α (ERα) expression are often more differentiated histologically than ERα-negative tumors, but the reasons for this difference are poorly understood. One possible explanation is that transcriptional cofactors associated with ERα determine the expression of genes which promote a more differentiated phenotype. In this study, we identify one such cofactor as coactivator-associated arginine methyltransferase 1 (CARM1), a unique coactivator of ERα that can simultaneously block cell proliferation and induce differentiation through global regulation of ERα-regulated genes. CARM1 was evidenced as an ERα coactivator in cell-based assays, gene expression microarrays, and mouse xenograft models. In human breast tumors, CARM1 expression positively correlated with ERα levels in ER-positive tumors but was inversely correlated with tumor grade. Our findings suggest that coexpression of CARM1 and ERα may provide a better biomarker of well-differentiated breast cancer. Furthermore, our findings define an important functional role of this histone arginine methyltransferase in reprogramming ERα-regulated cellular processes, implicating CARM1 as a putative epigenetic target in ER-positive breast cancers.
Letter: Lassa fever.
Authors: D W Atkinson
Journal: BMJ (1975)

crease in size within a 35-day period.Furthermore, it is incorrect to say that "the tumours appear to lose their property of metastasizing in the system."In June 1974 my colleagues and I reviewed our work at a Royal Society of Medicine meeting, during which we reported a case of metastatic growth of a melanoma to a mouse para- aortic node.We believe this was the first reported case of metastases in the T-B+ mouse.4We have subsequently reported metastases from human colon, rectum, and HeLa tumours, all to mouse lung.5These observations are comparatively recent and may in part be due to the use of mice from the specific-pathogen-free unit at Mill Hill.In conclusion, I cannot in principle see the objection to using this system for chemotherapeutic sensitivity studies of tumours.Wthy should it be necessary to establish that actual growth is occurring?After all, the T -B + mouse can be used to maintain tissues in vivo without having actual growth.In a pilot study my col- leagues and I examined the sensitivity of a breast tumour to chemotherapeutic agents and compared the treated mice with un- treated mice.During the study period, in excess of 40 days, the implanted tumours gradually regressed (we have demonstrated growth in other studies), but we compared the regression rates between the treated and untreated mice.Nobody would be foolish enough to suggest at this stage that the system should be used as the ultimate criterion for chemotherapeutic treatment.However, it can provide very useful guide- lines.Anything which can do that in a branch of medicine, which largely relies on trial and error cannot be a bad thing.-Iam, etc.,
MACOP-B Chemotherapy for the Treatment of Diffuse Large-Cell Lymphoma
Authors: Paul Klimo, Joseph M. Connors
Journal: Annals of Internal Medicine (1985)

Between April 1981 and May 1984, 61 patients with advanced diffuse large-cell lymphoma completed treatment with MACOP-B (methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin), an innovative pilot chemotherapy program emphasizing weekly treatment, antibiotic prophylaxis, daily corticosteroid treatments, and brief duration (12 weeks). Fifty-one patients (84%) achieved a complete response and 10 patients (16%) had a partial response. Over a median follow-up after treatment of 23 months, the actuarial overall survival for the entire group has been 76%; for complete responders the relapse-free survival has been 90%. Toxicity was modest with one treatment-related death and seven episodes of serious infection. The most frequent toxicity was mucositis. Thus, MACOP-B is an effective treatment for large-cell lymphoma that can be delivered in 12 weeks with an acceptable incidence of toxicity. This regimen can achieve results similar and possibly superior to those of other presently used regimens of longer duration.
Use of the signal-averaged electrocardiogram for predicting inducible ventricular tachycardia in patients with unexplained syncope: Relation to clinical variables in a multivariate analysis
Authors: Jonathan S. Steinberg, Eric Prystowsky, Roger A. Freedman, Fidela Moreno, Richard Katz, Jack Kron, Arlene Regan, Robert R. Sciacca
Journal: Journal of the American College of Cardiology (1994)
Seminars in Radiation Oncology
Authors: Robert E. Wallace
Journal: JAMA (1993)

A major goal of<i>Seminars in Radiation Oncology</i>, according to editor Joel E. Tepper, is to bridge the gap between the new and often controversial information published in peer-reviewed research journals and the clinical practice of the radiation oncologist. Journals like<i>Radiotherapy and Oncology, Radiation Medicine, and International Journal of Radiation Oncology, Biology, Physics</i>serve the vital role of bringing the results of current research to the radiation oncology community.<i>Seminars in Radiation Oncology</i>attempts to synthesize this new knowledge into a form that facilitates its application to cancer radiotherapy. In addition, future issues of this new review journal will discuss the impact of other disciplines, such as surgery and chemotherapy, on radiation oncology. New developments from the laboratory that relate to clinical practice will also be represented. The editorial board is composed of recognized experts in the field. All of them serve on the editorial boards of the major
Effects of topical glucocorticoids on in vitro lactoferrin glandular secretion: Comparison between human upper and lower airways
Authors: Jordi Roca-Ferrer, Joaquim Mullol, María Pérez, Antoni Xaubet, Laureano Molins, Josep de Haro, James Shelhamer, César Picado
Journal: Journal of Allergy and Clinical Immunology (2000)
Prevention of relapses in systemic lupus erythematosus
Authors: H. Bootsma, P. Spronk, G. de Boer, P. Limburg, C. Kallenberg, R. Derksen, J. Wolters-Dicke, F. Gmelig-Meyling, L. Kater, J. Hermans
Journal: The Lancet (1995)
EBNA1-specific CD4+ T cells in healthy carriers of Epstein-Barr virus are primarily Th1 in function
Authors: Kara Bickham, Christian Münz, Ming Li Tsang, Marie Larsson, Jean-Francois Fonteneau, Nina Bhardwaj, Ralph Steinman
Journal: Journal of Clinical Investigation (2001)

The Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA1) maintains the viral episome in all host cells infected with EBV. Recently, EBNA1 was found to be the main EBV latency antigen for CD4+ T cells and could be recognized in cultures from all donors tested. We now identify a polarized Th1 phenotype and obtain evidence for its presence in vivo. When T cells were stimulated with dendritic cells infected with vaccinia vectors expressing EBNA1, 18 of 19 donors secreted IFN-γ, whereas only two of 19 secreted IL-4. Magnetic selection was then used to isolate cells from fresh blood based on EBNA1-induced cytokine production. Specific IFN-γ CD4+ cell lines were established from six of six donors and IL-4 lines from three of six. Only the Th1 lines specifically lysed targets expressing three different sources of EBNA1 protein. When the IgG isotype of EBNA1 plasma Ab’s was tested, most specific Ab’s were IgG1 and of a high titer, confirming a Th1 response to EBNA1 in vivo. Ab’s to other microbial antigens generally were not skewed toward IgG1. Given emerging evidence that Th1 CD4+ T cells have several critical roles in host defense to viral infection and tumors, we propose that EBNA1-specific CD4+ Th1 cells contribute to resistance to EBV and EBV-associated malignancies.
Evaluation of platelets in heart failure: Is platelet activity related to etiology, functional class, or clinical outcomes?
Authors: Paul A. Gurbel, Wendy A. Gattis, Sergey F. Fuzaylov, Laura Gaulden, Vic Hasselblad, Victor L. Serebruany, Christopher M. O'Connor
Journal: Journal of the American College of Cardiology (2003)
1059-30 Effect of nesiritide on renal function after implantation of the abiocor total artificial heart
Authors: Reynolds M Delgado, Branislav Radovancevic, Biswajit Kar, Yasmin Wadia, Nancy Scroggins, Timothy J Myers, Igor D Gregoric, O.H Frazier
Journal: Journal of the American College of Cardiology (2004)
Regulatory mechanisms of growth hormone secretion are sexually dimorphic.
Authors: C A Jaffe, B Ocampo-Lim, W Guo, K Krueger, I Sugahara, R DeMott-Friberg, M Bermann, A L Barkan
Journal: Journal of Clinical Investigation (1998)

Sexually dimorphic growth hormone (GH) secretory pattern is important in the determination of gender-specific patterns of growth and metabolism in rats. Whether GH secretion in humans is also sexually dimorphic and the neuroendocrine mechanisms governing this potential difference are not fully established. We have compared pulsatile GH secretion profiles in young men and women in the baseline state and during a continuous intravenous infusion of recombinant human insulin-like growth factor I (rhIGF-I). During the baseline study, men had large nocturnal GH pulses and relatively small pulses during the rest of the day. In contrast, women had more continuous GH secretion and more frequent GH pulses that were of more uniform size. The infusion of rhIGF-I (10 microg/kg/h) potently suppressed both spontaneous and growth hormone-releasing hormone (GHRH)-induced GH secretion in men. In women, however, rhIGF-I had less effect on pulsatile GH secretion and did not suppress the GH response to GHRH. These data demonstrate the existence of sexual dimorphism in the regulatory mechanisms involved in GH secretion in humans. The persistence of GH responses to GHRH in women suggests that negative feedback by IGF-I might be expressed, in part, through suppression of hypothalamic GHRH.
Don't interrupt my homework
Authors: T Greenhalgh
Journal: BMJ (1994)

“You're a GP, a writer, a clinical tutor, and a research fellow. You must have a very good nanny,” said one of my patients the other day.

Actually, I manage with a part time child-minder and a lass who comes in once a week to bath my boys for a tenner. I do the school run every day and hit the supermarket at off peak hours. If this is making you jealous, remember that much of the time when I am assumed to be off duty, I am sitting in my study with a Do Not Disturb sign on the door. …
IMPACT OF OPTIMAL STENT EXPANSION ON OUTCOMES OF DRUG-ELUTING STENT IMPLANTATION FOR SMALL CORONARY VESSELS(≤2.75MM) AS ASSESSED WITH INTRACORONARY ULTRASOUND
Authors: Hiroshi YamaguchI, Nobuhiko Atsuchi, Junichiro Takaoka, Akihiro Miyamura, Takahiro Shirasawa, Ryuma Nakao, Junko Yoshinaga, Yoshihiko Atsuchi
Journal: Journal of the American College of Cardiology (2010)
TETANUS: ITS PREVENTION AND TREATMENT BY MEANS OF ANTITETANIC SERUM
Authors: A. MacConkey
Journal: BMJ (1914)

A 43 year old woman in remission from acute myeloid leukaemia developed abdominal pain, severe melaena, diarrhoea and gram-negative septicaemia whilst severely pancytopenic following consolidation chemotherapy. Subsequently, serial abdominal X-rays showed a progressive toxic megacolon. Conservative management was attempted but, because of radiological evidence of increasing colonic dilatation and incipient perforation, an emergency defunctioning colostomy was performed. The patient recovered and 2 months later the caecostomy was reversed and a right hemicolectomy performed. This first described case of toxic megacolon following leukaemia treatment is compared with three previously described cases following cytotoxic chemotherapy for other conditions.