tbuckley/cabot-search huggingface dataset:
Trojan-Horse Lymphocytes
Authors: Robert S. Schwartz
Journal: New England Journal of Medicine (1974)

This week's issue of the Journal brings news of two infants in whom fatal graft-versus-host disease developed after intrauterine and exchange transfusions for hemolytic disease of the newborn. The Journal of December 6, 1973, published as its weekly clinicopathological exercise the case of a 27-year-old man who had the nephrotic syndrome with Hodgkin's disease.1 Although the diseases affecting the infants and the man hardly seem related, I shall attempt to link them by a common mechanism.Ordinarily, transplanted foreign cells or tissues are rejected by an immune response engendered in the recipient by antigens of the graft. However, if the . . .
Clinical Outcomes Associated With Procalcitonin Algorithms to Guide Antibiotic Therapy in Respiratory Tract Infections
Authors: Philipp Schuetz, Matthias Briel, Beat Mueller
Journal: JAMA (2013)

In patients with respiratory tract infection, is measurement of procalcitonin to guide antibiotic prescriptions associated with reduced antibiotic exposure without increases in all-cause mortality or treatment failure?The measurement of procalcitonin to guide initiation and duration of antibiotic treatment in patients with respiratory tract infections of varying severity is associated with lower antibiotic exposure without increasing all-cause mortality or treatment failure.
Abstract 5762: Role of BMP7 in dormancy and recurrence of prostatic tumor stem cell in the bone metastasis
Authors: Aya Kobayashi, Hiroshi Okuda, Eiji Furuta, Puspa R. Pandey, Misako Watabe, Sudha K. Pai, Fei Xing, Wen Liu, Kounosuke Watabe
Journal: Cancer Research (2010)

Abstract Prostate cancer is becoming a curable disease when it is diagnosed at an early stage. However, even those patients who have localized cancer and have been “successfully” treated with surgery often experience recurrent disease after many years of dormancy. In the case of prostate cancer, bone is the most common metastatic site which affects approximately 70% of patients with advanced disease. The growth of the tumor cells in the bone is generally slow and they often become dormant until an appropriate microenviroment is established for their re-growth. How these metastatic tumor cells become dormant and how they recur at the target organs is virtually unknown. To address this critical question, we have studied an interaction of prostate cancer cell (PC3mm) and bone stromal cell (HS5). Our data indicate that the conditioned medium of HS5 cells was able to induce growth arrest and senescence to prostate cancer cells through activation of p38 MAP kinase. Western blot, qRT-PCR and reporter assay showed that this effect was mediated by induction of the tumor metastasis suppressor gene, N-myc downstream regulated gene 1 (NDRG1). We found that this secretory factor is bone morphogenetic protein 7 (BMP7) and that a specific inhibitor of p38 significantly abrogated up-regulation of NDRG1 by BMP7, suggesting that BMP7 induces NDRG1 through activation of p38. We also found that BMP7 significantly activated p21 and that this effect was inhibited by siRNA to NDRG1. Importantly, our results indicate that BMP7 was able to induce senescence to PC3mm cell; however, this senescence was reversible and the tumor cells re-gained the ability of their growth upon withdrawal of BMP7, suggesting that BMP7-induced senescence is reversible. Notably, our results of the existing database analysis indicate that the expression level of BMPR2, one of the BMP7 receptors, showed inverse correlation with bone metastasis and recurrence of prostate cancer. Furthermore, we isolated tumor stem population from PC3mm, and examined the effect of BMP7 on these cells. BMP7 indeed induced p38, NDRG1 and p21 in the prostate tumor stem cells. BMP7 also significantly suppressed sphere forming ability of the tumor stem cells followed by activation of NDRG1 and this effect was reversed by withdrawal of BMP7. These results suggest that the BMP7-NDRG1axis plays a critical role in the regulation of dormancy and recurrence of prostate tumor cells in bone metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5762.
Routine Prenatal Screening for Hepatitis B Surface Antigen
Authors: Mark A. Kane
Journal: JAMA (1988)

Transmission of the hepatitis B virus (HBV) during the perinatal period leads to the most devastating consequences of HBV infection. Women who test positive for hepatitis B surface antigen (HBsAg) at the time of delivery and who have hepatitis B e antigen in their sera have a 70% or greater chance of transmitting infection to their newborn infants. At least 90% of these infected infants become HBV chronic carriers. These HBV-carrier children have a 25% lifetime risk of dying from primary hepatocellular carcinoma or cirrhosis, usually during adulthood.<sup>1</sup>In addition, they serve as a reservoir of HBV infection in their families and communities. Many become carrier mothers themselves and perpetuate the cycle of perinatal transmission. Fortunately, treatment of these newborns shortly after birth with a combination of hepatitis B immune globulin and hepatitis B vaccine is 85% to 95% effective in preventing development of the HBV—chronic carrier state.<sup>2</sup>
Cell-intrinsic regulation of murine dendritic cell function and survival by prereceptor amplification of glucocorticoid
Authors: Annelise Soulier, Sandra M. Blois, Shivajanani Sivakumaran, Farnaz Fallah-Arani, Stephen Henderson, Barry Flutter, Elizabeth H. Rabbitt, Paul M. Stewart, Gareth G. Lavery, Clare Bennett, S. John Curnow, Ronjon Chakraverty
Journal: Blood (2013)
Estrogen inhibits mechanical strain-induced mitogenesis in human vascular smooth muscle cells via down-regulation of Sp-1
Authors: S Ling
Journal: Cardiovascular Research (2001)

Objective: The cellular basis of the cardioprotective effects of estrogen are largely unknown. An inhibitory effect on vascular smooth muscle (VSM) growth has been proposed. We examined the effect of 17β-estradiol (E2) on mechanical strain-induced mitogenesis in human fetal VSM cells. Methods and results: Cells were grown on fibronectin-coated plates with silicone-elastomer bottoms, and exposed to cyclic mechanical strain (60 cycles/min), with and without E2 (1 nmol/l), for 48 h. [3H]-Thymidine incorporation was measured during the last 6 h. Strain induced 1.5–2 fold increases in DNA synthesis that were attenuated by antibodies to platelet-derived growth factor (PDGF) AA and BB. Strain also induced increases both in mRNA and protein levels of Sp-1, a transcription factor that binds to the PDGF-A gene promoter site. E2 attenuated strain-induced mitogenesis, and also increases in mRNA and protein levels of Sp-1. The estrogen receptor (ER) antagonist ICI 182,780 (100 nmol/l) reversed the inhibitory effect of E2 on strain-induced increases in DNA synthesis and Sp-1 protein. RT-PCR analysis showed presence of both ER-α and -β in these cells. Conclusions: Estrogen inhibits strain-induced mitogenesis in human VSM cells via an ER mediated process involving down-regulation of the transcription factor Sp-1.
Responsibility for ancillary care in clinical trials: Finding out what participants think may be way forward
Authors: Ike Anya
Journal: BMJ (2004)

Firm foundation for senior house officers Five years is long enoughEditor-The editorial by Gallen and Peile signals anything but a firm foundation for training junior doctors. 1 The first foundation year will essentially be an extension of undergraduate training, its doctors allowed only to observe medical practice.And doctors in foundation year 2 will be "career tourists," spending too little time in each specialty to be able to offer much service in return.Medical educationalists should realise that nurses and other paramedical groups are encroaching on traditional medical practice and do not seem to need the sort of extended training we demand of medical students.For example, a six week course apparently enables paramedics to administer safely almost all drugs used in emergency practice.By contrast we seem intent on postponing the time at which our bright and enthusiastic young doctors can start treating patients.Five years is quite long enough to learn the theory of medicine.After that, the sooner young doctors are allowed to start treating patients, in a supervised setting, the better.
Cachectin (Tumor Necrosis Factor): A Macrophage Hormone Governing Cellular Metabolism and Inflammatory Response
Authors: BRUCE BEUTLER, ANTHONY CERAMI
Journal: Endocrine Reviews (1988)

DURING the past few years, a variety of cytokines have been isolated and synthesized in abundance by molecular cloning techniques. One of these, a molecule known as "cachectin" or "tumor necrosis factor," has emerged as an important component of the inflammatory response. Cachectin is produced by extravascular effector cells (principally macrophages) in response to invasive stimuli, and circulates throughout the body. Cachectin activates neutrophils, alters the properties of vascular endothelial cells, and regulates the metabolic activities of a variety of other tissues as well. Through its multiple effects, cachectin mediates many of the effects of endotoxin, both untoward and beneficial. Moreover, it induces a state of anorexia and wasting similar to that observed in chronic neoplastic and infectious diseases. Thus, this single protein mediator may play a central role in the pathogenesis of diverse disease states. Cachectin, an important factor in numerous physiological processes, was independently isolated by workers concerned with very different biological phenomena. As "cachectin," it was isolated as a result of inquiry into the mechanism of wasting in chronic disease; as "tumor necrosis factor," it was isolated as a result of inquiry into the cause of tumor necrosis occurring in the setting of infection. These two lines of investigation, and the molecule that they disclosed, are reviewed here.
The Nature and Nurture of Twins
Authors: Susan Reitz O'Neil
Journal: JAMA (1985)

<i>The Nature and Nurture of Twins</i>is an excellent review of the subject of twins, with additional notes on multiple births. In her preface, Dr Bryan states that practicing physicians, not to mention parents of twins, have few reference sources and do not know what problems to anticipate with twins. Dr Bryan has had an opportunity to work with many families of twins and from these experiences draws much of her information and advice. The book, although aimed at pediatricians and practitioners seeing children, could also be useful to parents, with its informational advice on feeding, care, preschool development, school considerations, and management of illness and death in a twin. The sections about history and customs surrounding twins are interesting in general. Some chapters, such as those about biology of twinning and zygosity, are more detailed, less anecdotal, and more directed at medical audiences, although some parents will also find
Placebo controlled trials are needed to provide data on effectiveness of active treatment
Authors: D B Double
Journal: BMJ (1996)

ing the dataset specification; training and continuing support of those who collect data; and the development and testing of in house database and reporting systems.To date, 108 units have been recruited-that is, 46% of the units in England and Wales.5With a remit to be self financing within two years, the audit is run on a cost recovery basis and makes a small annual charge to each participating unit.It should be noted that the extraction, collection, and entry of accurate data require resources for staff, software, and hardware.The total cost, however, is barely 1% of the annual budget for an average intensive care unit.The centre was established as a charitable company separate from the society so that it could pro- vide independent and objective audit and research into intensive care.As well as providing feedback to units for audit purposes, the resultant database will be a valuable resource for research.Through the centre's work with the Cochrane Collaboration, identifying and systematically reviewing trials relevant to intensive care, we hope to contribute to the scientific evidence on which future practice in intensive care should be based.Without a role model to follow, we have learnt several lessons along the way-for example, how to deal with confidentiality and the ownership of data.If the orthopaedic surgeons take up Sochart and colleagues' call we would be happy to share our experiences.
Results from a Phase 2 Study of Ruxolitinib or Placebo with Capecitabine as Second-Line Therapy in Patients with Metastatic Pancreatic Cancer: The Recap Trial
Authors: H. Hurwitz, N. Uppal, S.A. Wagner, J. Bendell, B.J. Thaddeus, S. Wade, J. Nemunaitis, P. Stella, J.M. Pipas, Z. Wainberg, R. Manges, W. Garrett, D. Hunter, J. Clark, L. Leopold, R. Levy, V. Sandor
Journal: Annals of Oncology (2014)
DEVELOPMENT OF ANTI-IDIOTYPIC ANTIBODIES AGAINST TUMOUR ANTIGENS AND AUTOANTIGENS IN OVARIAN CANCER PATIENTS TREATED INTRAPERITONEALLY WITH MOUSE MONOCLONAL ANTIBODIES
Authors: NigelS. Courtenay-Luck, AgamemnonA. Epenetos, GregoryB. Sivolapenko, JuliaR. Barkans, Mark Larche, MaryA. Ritter
Journal: The Lancet (1988)
IgE, IgG1, and IgG4 antibody responses to <i>Blomia tropicalis</i> in atopic patients
Authors: E. A. L. Pereira, D. A. O. Silva, J. P. Cunha‐Júnior, K. C. Almeida, R. Alves, S. J. Sung, E. A. Taketomi
Journal: Allergy (2005)

Background: Allergens from house dust mites (HDMs), Dermatophagoides pteronyssinus and Blomia tropicalis are clinically relevant in atopic respiratory diseases in tropical countries. Aims of the study: To evaluate immunoglobulin (Ig)E, IgG1, and IgG4 antibody responses to B. tropicalis in Brazilian atopic patients. Methods: About 110 patients with allergic rhinitis with/without asthma and 33 control subjects underwent skin prick testing (SPT) with HDM extracts, and their sera were tested for IgE and IgG subclass antibodies to D. pteronyssinus and B. tropicalis by enzyme‐linked immunosorbent assay (ELISA) and immunoblotting. Results: Most patients (56%) had positive SPT to B. tropicalis extract ( B. tropicalis + group), although 51% were reactive to both B. tropicalis and D. pteronyssinus and 6% were sensitized to B. tropicalis only. IgE‐ELISA detected 43% B. tropicalis positivity with high‐specific IgE levels in B. tropicalis + patients. Specific IgG4 levels were higher in B. tropicalis + than B. tropicalis − groups and correlated with specific IgE levels. The IgG1 levels to B. tropicalis were higher in patients than controls. The major allergenic B. tropicalis components recognized by B. tropicalis + patient sera were the 54, 66, and 68 kDa proteins. The IgG4‐binding protein profiles closely resembled that of IgE. The IgG1 antibodies recognizing multiple B. tropicalis protein species were detected in sera of all three patient groups. Conclusions: A large percentage of our allergic patients are B. tropicalis +. They are more frequently sensitized to high‐molecular weight (HMW) B. tropicalis components than the major low‐molecular weight (11–15 kDa) allergens detected in other studies. The results suggest that HMW B. tropicalis antigenic components are potential candidates for evaluating allergen exposure and sensitization, and for immunotherapy treatment.
Bulboventricular foramen size in infants with double-inlet left ventricle or tricuspid atresia with transposed great arteries: Influence on initial palliative operation and rate of growth
Authors: Abraham Matitiau, Tal Geva, Steven D. Colan, Thierry Sluysmans, Ira A. Parness, Philip J. Spevak, Mary Van Der Velde, John E. Mayer, Stephen P. Sanders
Journal: Journal of the American College of Cardiology (1992)
Expression of Bcl-2 and Bax in cultured normal human keratinocytes and melanocytes: relationship to differentiation and melanogenesis
Authors: S. SERMADIRAS, M. DUMAS, R. JOLY-BERVILLIE, F. BONTÉ, A. MEYBECK, M.H. RATINAUD
Journal: British Journal of Dermatology (1997)

Keratinocyte differentiation and melanogenesis are two major cellular processes by which the epidermal compartment of the skin acquires its protective properties. Bcl-2; an oncoprotein involved in the regulation of apoptosis, has been shown to be expressed by keratinocytes and melanocytes. To determine whether Bcl-2 and Bax, a protein which heterodimerizes with Bcl-2, may control these epidermal functions, we investigated the expression of these two oncogenes in cultivated human keratinocytes and melanocytes from the same donors, respectively induced to differentiate and to produce melanin. As determined by cytometry, we observed that these two cell types constitutively express the two proto-oncogenes. Quantification of Bcl-2 antigen sites per cell showed that Bcl-2 expression is higher in keratinocytes than in melanocytes. An increase in transglutaminase activity, a marker of keratinocyte terminal differentiation initiating cornified envelope formation, was accompanied by a decrease in Bcl-2 levels without significant modification of Bax expression. In melanocyte cultures, stimulation of the dopa-oxidase pool, a key enzyme in melanin synthesis, paralleled Bcl-2 down-regulation and Bax up-regulation. This led us to conclude that the expression of these two oncogenes and their cellular ratio are closely involved in keratinocyte differentiation and melanogenesis.
Abstract LB-227: Receptor tyrosine kinase phosphorylation: Simultaneous detection of 10 kinases upon inhibitor treatment
Authors: Tanja Henzler, Stefanie Pohl, Nicole Schneiderhan-Mara, Stefanie Rimmele, April Livengood, Robert Kovelman, Thomas Herget
Journal: Cancer Research (2010)

Abstract Receptor tyrosine kinases have been shown to be major pharmaceutical targets involved in disease states such as diabetes and cancer. Target driven therapeutics like small molecules or monoclonal antibodies are already in clinical use and have tremendous influence on new cancer therapies. In most cases either ligand binding to the extracellular domain followed by receptor dimerization or ATP binding to the intracellular kinase domain is inhibited. However, it is still challenging to gain specificity of those inhibitors for certain receptor tyrosine kinase targets. Bead-based assay technologies, such as the xMAP® platform, are ideal tools for the multiplex analysis of 5-20 proteins. Low sample volumes, simple assay protocols, flexibility and robustness are characteristics of bead-based assays that make them well suited for the immunological detection of bio marker and cell signaling proteins. In this presentation we will show results for the simultaneous detection of the ten most relevant receptor tyrosine kinases. The expression profile of more than 50 cell lines as well as breast tumor samples were evaluated with this powerful multiplex tool in a very robust and convenient way. Inhibitor profiling of small molecules under physiological conditions on ten receptor tyrosine kinases will be demonstrated by the detection of their phospho-Tyrosine level. These specificity profiles will help to improve the drug development process and to obtain potentially better drugs in future. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-227.
Surgical treatment of chronic hidradenitis suppurativa: CO2 laser stripping-secondary intention technique
Authors: J. LAPINS, J.A. MARCUSSON, L. EMTESTAM
Journal: British Journal of Dermatology (2006)

The objective of our study was to evaluate a surgical method of management of patients with hidradentitis suppurativa (HS), using a CO2 laser technique for stepwise horizontal vaporization and peroperative monitoring of the removal of diseased tissue. Twenty-four patients were selected for treatment, 21 women and three men, who had suffered from HS for a mean of 13 years (range 1–28 years) and experienced more than three recurrences of suppurating lesions during the year prior to entering the study. The mean follow-up time after CO2 laser surgery was 27 months (range 15–47 months), with clinical follow-up once or twice a week during the wound-healing period, and then at intervals of 1–3 months to evaluate recurrences and assess the end result. The patients' healing time was approximately 4 weeks (range 3–5 weeks). During the follow-up period two patients had recurrences in the treated areas. Twenty-two patients had no recurrences in the treated areas, but in four cases de novo suppurating lesions appeared 5–10 cm beyond the initial sites of surgery. Ten patients had exacerbations of HS lesion(s) in a region other than the treated site. Eight patients did not have any recurrences. Post-surgery results were satisfactory both cosmetically and with regard to quality of life. The CO2 laser stripping-secondary intention technique is a rapid, efficient, and economical method for the treatment of HS. It allows simple treatment of early lesions which would otherwise have been treated using less effective local conservative remedies.
Phase I Study of a Systemically Delivered p53 Nanoparticle in Advanced Solid Tumors
Authors: Neil Senzer, John Nemunaitis, Derek Nemunaitis, Cynthia Bedell, Gerald Edelman, Minal Barve, Robert Nunan, Kathleen F Pirollo, Antonina Rait, Esther H Chang
Journal: Molecular Therapy (2013)

Selective delivery of therapeutic molecules to primary and metastatic tumors is optimal for effective cancer therapy. A liposomal nanodelivery complex (scL) for systemic, tumor-targeting delivery of anticancer therapeutics has been developed. scL employs an anti-transferrin receptor (TfR), scFv as the targeting molecule. Loss of p53 suppressor function, through mutations or inactivation of the p53 pathway, is present in most human cancers. Rather than being transiently permissive for tumor initiation, persistence of p53 dysfunction is a continuing requirement for maintaining tumor growth. Herein, we report results of a first-in-man Phase I clinical trial of restoration of the normal human tumor suppressor gene p53 using the scL nanocomplex (SGT-53). Minimal side effects were observed in this trial in patients with advanced solid tumors. Furthermore, the majority of patients demonstrated stable disease. One patient with adenoid cystic carcinoma had his status changed from unresectable to resectable after one treatment cycle. More significantly, we observed an accumulation of the transgene in metastatic tumors, but not in normal skin tissue, in a dose-related manner. These results show not only that systemically delivered SGT-53 is well tolerated and exhibits anticancer activity, but also supply evidence of targeted tumor delivery of SGT-53 to metastatic lesions.
Congenital Rubella Syndrome in Late Infancy
Authors: Stanley A. Plotkin
Journal: JAMA (1967)

A group of 109 Philadelphia infants with congenital abnormalities presumably caused by rubella was analyzed for various features. Isolation data showed that only a few infants had virus present in the throat and cerebrospinal fluid by 1 year of age (9% and 4%, respectively). Recovery of virus from lens material obtained at surgery, however, was frequent, even in patients 18 months old. The neutralizing-antibody test was found useful in the retrospective diagnosis of rubella syndrome. A titer of 1:4 or greater in infants older than 6 months was 94% accurate in identifying intrauterine infection. The complement-fixation test was less useful.