tbuckley/cabot-search huggingface dataset:
Pretargeted α Emitting Radioimmunotherapy Using 213Bi 1,4,7,10-Tetraazacyclododecane-<b><i>N</i></b>,<b><i>N</i></b>′,<b><i>N</i></b>″,<b><i>N</i></b>‴-Tetraacetic Acid-Biotin
Authors: Zhengsheng Yao, Meili Zhang, Kayhan Garmestani, Donald B. Axworthy, Robert W. Mallett, Alan R. Fritzberg, Lou J. Theodore, Paul S. Plascjak, William C. Eckelman, Thomas A. Waldmann, Ira Pastan, Chang H. Paik, Martin W. Brechbiel, Jorge A. Carrasquillo
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The use of an α emitter for radioimmunotherapy has potential advantages compared with β emitters. When administered systemically optimal targeting of intact antibodies requires &amp;gt;24 h, therefore limiting the use of short-lived α emitters. This study investigated the biodistribution of bismuth-labeled biotin in A431 tumor-bearing mice pretargeted with antibody B3-streptavidin (B3-SA) and examined the therapeutic efficacy of the α emitter, 213Bi-labeled biotin. Experimental Design: Biotinidase-resistant 7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA)-biotin was radiolabeled with 205,206Bi or 213Bi. Treatment of tumor-bearing mice began by administration of B3-SA (400 μg) to target the tumor sites for 24 h. Then, an agent containing biotin and galactose groups was used to clear the conjugate from the circulation. Four h later, bismuth-radiolabeled DOTA-biotin was given, and biodistribution or therapy was evaluated. Dose escalation treatment from 3.7–74 MBq was performed, and the effects on tumors of different sizes were investigated. Tumor growth, complete blood cell counts, toxicity, and survival were monitored. Results: Radiolabeled biotin cleared rapidly. Rapid tumor uptake resulted in much higher tumor:nontumor targeting ratios than achieved with the directly labeled monoclonal antibody. Dose escalation revealed that 74 MBq caused acute death of mice, whereas 0.37–37 MBq doses inhibited tumor growth and prolonged survival significantly. Evidence of mild hematological toxicity was noted. At therapeutically effective doses renal toxicity was observed. Conclusions: 213Bi-DOTA-biotin, directed by the Pretarget method to tumor-targeted B3-SA, showed a therapeutic effect, although the therapeutic index was low. The source of the toxicity was most likely related to the renal toxicity.
Role of Chitinase 3–like-1 and Semaphorin 7a in Pulmonary Melanoma Metastasis
Authors: Bing Ma, Erica L. Herzog, Chun Geun Lee, Xueyan Peng, Chang-Min Lee, Xiaosong Chen, Sara Rockwell, Ja Seok Koo, Harriet Kluger, Roy S. Herbst, Mario Sznol, Jack A. Elias
Journal: Cancer Research (2014)

The prototypic chitinase-like protein Chi3l1 is induced in cancers and portends a poor prognosis, but whether it contributes to cancer progression is unknown. To address this gap in knowledge, we investigated the production of Chi3l1 in melanoma lung metastases. We found that Chi3l1 was induced during pulmonary melanoma metastasis and that this induction was regulated by the semaphorin Sema7a, interacting in stimulatory or inhibitory ways with its β1 integrin or Plexin C1 receptors, respectively. In mouse strains with genetic deletions of Chi3l1 or Sema7a, there was a significant reduction in pulmonary metastasis. Notably, antiserum raised against Chi3l1 or Sema7a phenocopied the reduction produced by genetic deletions. Melanoma lung metastasis was also decreased in the absence of IL13Rα2, a recently identified receptor for Chi3l1, consistent with a key role for Chi3l1 in melanoma spread. We confirmed roles for Sema7a and Chi3l1 in pulmonary metastasis of EMT6 breast cancer cells. Taken together, our studies establish a novel pathway through which Sem7a and its receptors regulate Chi3l1, revealing a host axis involving IL13Rα2 that plays a critical role in generating a pulmonary microenvironment that is critical to license metastasis.
Elimination of chronic viral infection by blocking CD27 signaling
Authors: Matthias Matter, Bernhard Odermatt, Hideo Yagita, Jean-Marc Nuoffer, Adrian F. Ochsenbein
Journal: The Journal of Experimental Medicine (2006)

Neutralizing antibody (nAb) responses to lymphocytic choriomeningitis virus (LCMV) in mice and immunodeficiency virus and hepatitis C virus in humans are usually weak and slow to develop. This may be the result of structural properties of the surface glycoprotein, a low frequency of B cells with neutralizing specificity, and the necessity of prolonged affinity maturation of specific nAbs. In this study, we show that during LCMV infection, CD27 signaling on CD4+ T cells enhances the secretion of interferon-γ and tumor necrosis factor-α. These inflammatory cytokines lead to the destruction of splenic architecture and immunodeficiency with reduced and delayed virus-specific nAb responses. Consequently, infection with the otherwise persistent LCMV strain Docile was eliminated after CD27 signaling was blocked. Our data provide a novel mechanism by which LCMV avoids nAb responses and suggest that blocking the CD27–CD70 interaction may be an attractive strategy to prevent chronic viral infection.
Biologic Characteristics of Some Mouse Mammary Tumor Viruses 2
Authors: Dan H. Moore, Jane A. Holben, Jesse Charney
Journal: JNCI Journal of the National Cancer Institute (1976)

The mammary tumor virus (MuMTV) in the milks of 7 mouse strains and substrains was titrated for infectivity in 4 strains. The data indicated that: 1) Each strain shed a different MuMTV and some genetic strains carried two MuMTV's, each discernible by its mouse strain preference in infectivity tests. 2) Less than 5% of RIIIf and about 10% of Af mice shed detectable MuMTV antigen in their milks after the third parturition. After the sixth parturition, 33% of RIIIf and 50% of Af, and after the ninth parturition, 60% of RIIIf and 90% of Af mice shed viral antigen in their milks. The MuMTV's in milks of high-parity mothers were most infectious in mouse strains different from those most susceptible to MuMTV in RIII and A milks of low-parity mothers. Therefore, RIII and A mice each harbored two viruses, one that was removed by foster-nursing and the other that was not. 3) The susceptibility incidence of RIIIfC57BL mice to RIII virus changed gradually from about 10% in 1970 to about 70% in 1975. Susceptibility of C57BL mice to RIII virus did not change appreciably over this period, and the natural tumor incidence in RIIIfC57BL remained unchanged (about 10%). In addition to their susceptibility to RIII virus, C57BL mice were also susceptible to GR virus; they were relatively resistant to other strains tested. They were especially resistant to RIIIf virus, to which Af and BALB/c mice were very susceptible. 4) Approximately 90% of C3HfC57BL and C3HfBALB/c mice shed antigen in their milks after the third parturition, although the tumor incidence was less and occurred later than in C3H mice. No clear-cut differences could be detected in infectivities between low-parity C3H milk and high-parity C3Hf milks tested in several assay strains.
Lymphocyte abnormalities in mycosis fungoides
Authors: RONA MacKIE, F.R. SLESS, REBECCA COCHRAN, MARIA SOUSA
Journal: British Journal of Dermatology (1976)

Fourteen patients with clinical and histological evidence of mycosis fungoides have undergone a series of immunological tests. Significant findings include the presence of low numbers of E and EAC rosette-forming cells in the peripheral circulation of the mycosis fungoides patients. Elevated levels of IgE were seen in five of the mycosis fungoides patients, and the mean IgE level was significantly higher than in the control series. Possible explanations of these findings are considered.
Matrix metalloproteinases and their inhibitors in gastric cancer
Authors: G I Murray, M E Duncan, E Arbuckle, W T Melvin, J E Fothergill
Journal: Gut (1998)

Background —The matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) are strongly implicated in tumour invasion and metastasis. Aims —To investigate the presence of individual MMPs and TIMPs in gastric cancer. Methods —The presence of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 was identified in a group of gastric cancers (n=74) by immunohistochemistry using monoclonal antibodies. These antibodies were effective on formalin fixed, paraffin wax embedded sections. Results —A large proportion (94%) of gastric cancers contained MMP-2; MMP-1 and MMP-9 were also detected in 73% and 70% of tumours respectively. MMP-3 was only present in 27% of tumours. MMP-1 and MMP-9 were found predominantly in intestinal type tumours. TIMP-1 and TIMP-2 were identified in 41% and 57% of tumours respectively. Immunoreactivity for individual MMPs or TIMPs was not identified in normal stomach. Conclusions —This study shows the presence of matrix metalloproteinases, particularly MMP-2, and TIMPs in stomach cancer. Antibodies which are effective in formalin fixed, paraffin wax embedded sections are useful for the identification of MMPs and TIMPs in diagnostic specimens.
Hic-5/ARA55, a LIM Domain–Containing Nuclear Receptor Coactivator Expressed in Prostate Stromal Cells
Authors: Marjet D. Heitzer, Donald B. DeFranco
Journal: Cancer Research (2006)

Abstract Prostate gland development and growth requires both androgen action and epithelial-stromal communications. In fact, androgen signaling through the androgen receptor (AR) may be important in both stromal and epithelial cells of the prostate. Because interaction of AR with the coactivator, Hic-5/ARA55, results in enhanced androgen-induced transcription, we analyzed Hic-5/ARA55 expression in prostate tissue sections from normal human donors and prostate cancer patients. In each sample, Hic-5/ARA55 expression was confined to the stromal compartment of the prostate. Furthermore, a prostate stromal cell line, WPMY-1 cells, expresses Hic-5/ARA55, which is localized both at focal adhesion complexes and within the soluble cytoplasmic compartment. The ability of Hic-5/ARA55 to shuttle between the nuclear and cytoplasmic compartments was revealed on inhibition of nuclear export with leptomycin B. Small interfering RNA ablation experiments established endogenous Hic-5/ARA55 as a coactivator for both viral and endogenous cellular AR-regulated genes. Finally, the mechanism of Hic-5/ARA55 coactivator activity in WPMY-1 cells was revealed by chromatin immunoprecipitation analysis that showed its androgen-dependent recruitment to the promoter of the stromal androgen-responsive keratinocyte growth factor gene. These data provide the first demonstration of a stromal-specific AR coactivator that has an effect on an androgen-regulated growth factor that is essential for stromal/epithelial cell communication in the prostate. (Cancer Res 2006; 66(14): 7326-33)
Government to revise health inequality proposals
Authors: Adrian O’Dowd
Journal: BMJ (2008)

Specific evidence based proposals to reduce health inequalities are to be announced this summer in a “refreshed” strategy from the UK government.

England’s deputy chief medical officer, Fiona Adshead, speaking at a conference last week, said that the revised strategy would contain proposals that would be costed and backed by real evidence.

Dr Adshead was speaking at the Tackling Health Inequalities to Meet 2010 Targets conference, organised by the health policy think tank the King’s Fund, in London.

The government had committed itself, she said, in the Tackling Inequalities: A Programme for Action strategy of 2003 to specific targets, such as a 10% reduction in inequalities by 2010, measured by infant mortality and life expectancy at birth.

But a recent report showed …
Validation of a score tool for measurement of histological severity in juvenile dermatomyositis and association with clinical severity of disease
Authors: Hemlata Varsani, Susan C Charman, Charles K Li, Suely K N Marie, Anthony A Amato, Brenda Banwell, Kevin E Bove, Andrea M Corse, Alison M Emslie-Smith, Thomas S Jacques, Ingrid E Lundberg, Carlo Minetti, Inger Nennesmo, Elisabeth J Rushing, Adriana M E Sallum, Caroline Sewry, Clarissa A Pilkington, Janice L Holton, Lucy R Wedderburn
Journal: Annals of the Rheumatic Diseases (2013)

Objectives To study muscle biopsy tissue from patients with juvenile dermatomyositis (JDM) in order to test the reliability of a score tool designed to quantify the severity of histological abnormalities when applied to biceps humeri in addition to quadriceps femoris. Additionally, to evaluate whether elements of the tool correlate with clinical measures of disease severity. Methods 55 patients with JDM with muscle biopsy tissue and clinical data available were included. Biopsy samples (33 quadriceps, 22 biceps) were prepared and stained using standardised protocols. A Latin square design was used by the International Juvenile Dermatomyositis Biopsy Consensus Group to score cases using our previously published score tool. Reliability was assessed by intraclass correlation coefficient (ICC) and scorer agreement (α) by assessing variation in scorers’ ratings. Scores from the most reliable tool items correlated with clinical measures of disease activity at the time of biopsy. Results Inter- and intraobserver agreement was good or high for many tool items, including overall assessment of severity using a Visual Analogue Scale. The tool functioned equally well on biceps and quadriceps samples. A modified tool using the most reliable score items showed good correlation with measures of disease activity. Conclusions The JDM biopsy score tool has high inter- and intraobserver agreement and can be used on both biceps and quadriceps muscle tissue. Importantly, the modified tool correlates well with clinical measures of disease activity. We propose that standardised assessment of muscle biopsy tissue should be considered in diagnostic investigation and clinical trials in JDM.
56 HBX BINDS IN VIVO ON THE HBV MINICHROMOSOME, MODIFIES THE EPIGENETIC REGULATION OF CCC-DNA FUNCTION AND POTENTIATES HBV REPLICATION
Authors: L. Belloni, T. Poliicino, L. Cimino, G. Raffa, G. Raimondo, M. Levrero
Journal: Journal of Hepatology (2008)
Secretome: clues into pathogen infection and clinical applications
Authors: Shoba Ranganathan, Gagan Garg
Journal: Genome Medicine (2009)

The secretome encompasses the complete set of gene products secreted by a cell. Recent studies on secretome analysis reveal that secretory proteins play an important role in pathogen infection and host-pathogen interactions. Excretory/secretory proteins of pathogens change the host cell environment by suppressing the immune system, to aid the proliferation of infection. Identifying secretory proteins involved in pathogen infection will lead to the discovery of potential drug targets and biomarkers for diagnostic applications.
Effect of a single inactivated poliovirus vaccine dose on intestinal immunity against poliovirus in children previously given oral vaccine: an open-label, randomised controlled trial
Authors: Jacob John, Sidhartha Giri, Arun S Karthikeyan, Miren Iturriza-Gomara, Jayaprakash Muliyil, Asha Abraham, Nicholas C Grassly, Gagandeep Kang
Journal: The Lancet (2014)
The Effects of Oxitropium Bromide on Exercise Performance in Patients with Stable Chronic Obstructive Pulmonary Disease
Authors: TORU OGA, KOICHI NISHIMURA, MITSUHIRO TSUKINO, TAKASHI HAJIRO, AKIHIKO IKEDA, TAKATERU IZUMI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The purpose of the present study was to compare the characteristics of three different exercise tests in evaluating the effects of oxitropium bromide on exercise performance. Thirty-eight males with stable chronic obstructive pulmonary disease (COPD) (FEV1 = 40.8 ± 16.5% predicted; mean ± SD) completed randomized, double-blind, placebo-controlled, crossover studies for each exercise test. The exercise tests were performed 60 min after the inhalation of either oxitropium bromide 400 μ g or placebo. The patients performed 6-min walking tests (6MWT) on Days 1 and 2, progressive cycle ergometry (PCE) on Days 3 and 4, and cycle endurance tests at 80% of the maximal workload of PCE on Days 5 and 6. Spirometry was conducted before and at 45 and 90 min after the inhalation. Oxitropium bromide significantly increased FEV1 as compared with placebo. Oxitropium bromide increased the endurance time significantly, by 19% (p < 0.001), and caused a small but significant increase in the 6-min walking distance by 1% (p < 0.05), but induced no significant increase in maximal oxygen consumption (V˙ o 2max) in PCE. The responses in these three exercise tests were different, and we conclude that the endurance test was the most sensitive in detecting the effects of inhaled anticholinergic agents on exercise performance in patients with stable COPD. An endurance procedure may be performed to detect clinical changes in evaluating the effects of oxitropium bromide on exercise performance.
Water jet skiing, a dangerous sport with inadequate policing!
Authors: Adnan A Faraj, H Prince, L Neumann, S Bollen
Journal: British Journal of Sports Medicine (2000)

Editor,—Water jet skiing is a popular international water sport. As yet there is no strict highway code to avoid accidents. We report two severe musculoskeletal injuries associated with this sport.

A 22 year old man presented with backwards and downwards pointed locked arms following bilateral anteroinferior fracture-dislocation of the shoulder with an associated brachial plexus lesion after …
Effect of ursodeoxycholic acid on bile acid metabolism in primary biliary cirrhosis
Authors: Ashok K. Batta, Gerald Salen, Renu Arora, Sarah Shefer, Stephen G. Tint, John Abroon, David Eskreis, Seymour Katz
Journal: Hepatology (1989)

We have compared the effect of ursodeoxycholic acid with placebo on the clinical state, blood liver chemistries and serum and urinary bile acids in four patients with primary biliary cirrhosis. All parameters were evaluated monthly, and bile acid composition was measured by capillary gas-liquid chromatography. At the time of admission, all patients showed intense pruritus, and their serum alkaline phosphatase, AST and ALT levels were elevated 4.3, 2.7 and 2.3 times over control values. Serum bile acids were elevated almost 38-fold with 2.5 times more cholic acid than chenodeoxycholic acid. Urinary bile acid output was elevated 28 times the control values, and 36% were 1β-hydroxycholic acid, 1β-hydroxydeoxycholic acid and hyocholic acid (3α,6α,7α-trihydroxy-5β-cholanoic acid). Three months of placebo administration did not significantly affect the clinical or biochemical presentations, and the serum and urinary bile acid composition did not change. In contrast, ursodeoxycholic acid feeding (12 to 15 mg per kg per day) for 6 months abolished pruritus in two and lessened itching in two subjects and reduced serum alkaline phosphatase, AST and ALT levels by 21, 35 and 47%, respectively. The mean values for the total serum bile acid concentrations in these patients declined 26% from the pretreatment value, but the proportion of ursodeoxycholic acid increased from 3 to 40% of the total bile acids; thus, total fasting serum endogenous bile acid levels decreased almost 50%. Similar changes were noted in the urinary bile acids, in which ursodeoxycholic acid became the major bile acid, and approximately 18% were hydroxylated at C-1, C-6 and C-21. These results demonstrate that, compared with placebo, ursodeoxycholic acid significantly lowers serum and urinary bile acids in primary biliary cirrhosis and produces considerable clinical and biochemical improvement.
Medical Students View Clinical Psychiatry
Authors: SIDNEY L. WERKMAN, STEPHEN LANDAU, HAROLD WAKEFIELD
Journal: American Journal of Psychiatry (1973)

To investigate the relevance of various components of psychiatric teaching to the later practice of medicine, the authors asked 126 medical students to rate their perceptions of clinical psychiatric work and to assess their view of psychiatry before and after a clerkship. The students rated their experiences in descending order of usefulness as follows: outpatient treatment, emergency service, didactic seminar, child psychiatry, and inpatient treatment. They also recorded statistically significant changes in their perceptions of themselves with regard to psychiatric patients as they gained clinical experience.
After the gold rush? A systematic and critical review of general medical podcasts
Authors: Paul Wilson, Mark Petticrew, Alison Booth
Journal: Journal of the Royal Society of Medicine (2009)

Summary Objectives Podcasts are increasingly used to enhance many forms of research communication and education. We set out to assess the extent of this podcast revolution by identifying and critically describing the content and quality of podcast services provided by leading general medical journals. Methods Summary of general and internal medicine journal podcasts identified in April 2008 by means of web-searching, with a brief commentary on their content and quality. Results Of the top 100 general medical and internal journals as ranked by impact factor only eight offer a regular podcast. The technical quality of most is of an acceptable but not of a high standard. The mode of delivery and resulting listening experience is variable with those utilizing an interview format more interesting to listen to than those reliant upon a single voice. Conclusions General medical podcasts are potentially a valuable resource for providing a digestible overview of the latest research, and for providing an opportunity to dip into areas outside one's own core interests. Although they represent a novel use of technology for disseminating knowledge, uptake has been limited and the quality of the listening experience is variable.
Epidemiological and virological assessment of influenza activity in Europe during the 2003-2004 season
Authors: A. Meijer, W.J. Paget, T.J. Meerhoff, C.S. Brown, L.E. Meuwissen, J. van der Velden
Journal: Eurosurveillance (2005)

The 2003-2004 influenza season in Europe was dominated by the spread of the new drift variant A/Fujian/411/2002 (H3N2)-like virus which was not perfectly matched with the A(H3N2) component of the influenza vaccine. Sporadic cases of this virus were detected in Europe at the end of the 2002-2003 season and influenza activity associated with this virus began relatively early during the 2003-2004 season. Generally, influenza activity first occurred in the west of Europe (Ireland, the United Kingdom and the Iberian Peninsula) in October/November and gradually moved east across Europe, affecting Latvia, Lithuania and Poland during the months of January and February 2004. In general, the intensity of clinical activity was higher than during the 2002-2003 season (in 13 out of 20 networks) and, in countries reporting age specific data, the highest consultation incidences were observed among children aged 0-14. However, despite the emergence of the A(H3N2) drift variant, clinical incidences were not especially high compared with historical data. The composition of the 2004-2005 influenza vaccine has been modified compared with the 2003-2004 season and includes an A/Fujian/411/2002 (H3N2)-like virus strain and a new B virus strain (a B/Shanghai/361/2002-like virus).