tbuckley/cabot-search huggingface dataset:
Investigation of a Researcher's Death Due to Septicemic Plague
Authors: Karen M. Frank, Olaf Schneewind, Wun-Ju Shieh
Journal: New England Journal of Medicine (2011)

This letter identifies the death of a researcher from infection with disseminated Yersinia pestis, which he was working with in the lab. It was subsequently determined that he had hemochromatosis, a condition that may have increased his susceptibility to this infection.
PTH-094 Faecal Calprotectin Testing in Primary and Secondary Care – are the Current Manufacturer’S Cut-Off Levels Clinically Useful?
Authors: S H Lee, H Mainman, H Borthwick, A Dhar
Journal: Gut (2013)

<h3>Introduction</h3> Faecal Calprotectin (FC) is a protein complex found in high concentrations in neutrophils and is released within the bowel when inflammation occurs. It can be measured quantitatively using ELISA and is very sensitive and specific in discriminating inflammatory from non-inflammatory pathologies causing diarrhoea. The manufacturer recommends a positive stool FC test (&gt; 60µg/g) to be indicative of inflammation and further investigations (e.g. endoscopy, histology and imaging) and referral to a Gastroenterology clinic is advised. <h3>Methods Aims:</h3> To determine whether the manufacturer’s cut-off levels for referral (&gt; 60µg/g) are clinically useful in making a positive diagnosis in patients presenting with chronic diarrhoea.<b>Methods</b>: We analysed the outcome of 122 FC test results done in primary and secondary care during a 3 month period from October to December 2011 performed on patients who presented with chronic diarrhoea without a pre-existing diagnosis of Inflammatory Bowel Disease (IBD). According to manufacturer’s guidance, a FC result of &gt; 60µg/g was considered positive and ≤60µg/g negative. Positive FC patients were seen in a Gastroenterology Clinic and investigated appropriately. The primary outcome of this study was to record the final diagnosis arising out of FC testing and investigations thereof. Secondary outcomes were to correlate FC levels to the final diagnosis. <h3>Results</h3> Of 122 FC tests, 41% (n = 51) were read as positive vs. 58% (n = 71) negative. 19/51 (37%) FC positive patients had a positive organic diagnosis (IBD = 9, Diverticulosis = 5, Colonic Polyps = 3, Infective colitis = 1 and Chronic Pancreatitis = 1) while the remaining 32 pts (63%) were given a diagnosis of functional bowel disorder after investigations. Of 71 patients testing negative on FC, 94% (n = 67) had functional bowel disorder; only 6% (n = 4) were found to have an organic condition, none of them IBD. This correlates with a positive predictive value of 37% and a negative predictive value of 94% for organic disease. The FC levels of those tested positive with a diagnosis of functional bowel disorder ranged from 61 – 547µg/g (mean 153µg/g) whereas FC values of those with organic conditions ranged from 63 – 1573µg/g (mean 746µg/g). <h3>Conclusion</h3> The current manufacturer’s cut-off at &gt; 60µg/g is not clinically useful to diagnose an organic bowel pathology and further studies are needed to determine the true cut off value for a higher yield of a positive diagnosis. Cost effectiveness studies are also needed to determine referral cut off values. <h3>Disclosure of Interest</h3> S. Lee: None Declared, H. Mainman: None Declared, H. Borthwick: None Declared, A. Dhar Grant/Research Support from: CLRN, NIHR, Speaker bureau with: Warner Chilcott UK, Shire Pharmaceuticals
MS-27 * THE IMPACT OF HYPOFRACTIONATED LINAC-BASED STEREOTACTIC RADIOSURGERY UPON EARLY AUDITORY FUNCTIONS IN THE TREATMENT OF VESTIBULAR SCHWANNOMAS
Authors: F. Wang, A. Roy, R. Badkul, P. John, P. Kumar, H. Staecker
Journal: Neuro-Oncology (2014)

PURPOSE: To determine the impact of hypofractionated stereotactic radiotherapy (fSRT) scheme upon early auditory functions in the treatment of vestibular schwannomas (VSs). MATERIALS AND METHODS: 21 VS patients treated with a Linac-based frameless fSRT to 25 Gy in 5 daily fractions were retrospectively reviewed. Serial audiometry tests including auditory thresholds and speech discrimination (SD) were conducted prior to fSRT and then at regular intervals post-fSRT to determine the impact of our fSRT scheme on the patient's hearing function. Radiation doses to tumor (conformity index) and cochlea (dose to modiolus, maximal dose and V10) were measured for their impact on the auditory function. RESULTS: There was no tumor recurrence with a median follow-up of 17 months (range, 4-34 mos.). Gross tumor volume ranged from 0.15 to 6.1 cm3 with a mean of 1.47 cm3. Average conformity index (CI) of fSRT was 1.29 ± 0.32. The mean dose to the modiolus of the cochlea, mean of maximal dose and mean of V10 of the cochlea (volume of cochlea received 10 Gy or more) were 16.28 Gy, 23.52 Gy and 87.62%, respectively. There was 7- 8 dBs increase of pure tone average on lower (200, 500 and 1000 Hz) and higher frequency (4000 and 8000 Hz) after fSRT. The average of SD was decreased from 62% to 51% after treatment, which was not statistically significant. A weak correlation between the cochlea dose (modiolus dose and cochlea maximal dose) and the change of higher frequency pure tone average (4000 and 8000 Hz) was observed with a coefficient of 0.48. CONCLUSION: In contrast to literature report of a significant change of pure tone average in the first 12 months after Gamma knife treatment, we observed no significant pure tone average decline but SD decline after fSRT on VS patients.
Physical Forces and Airway Remodeling in Asthma
Authors: Daniel J. Tschumperlin
Journal: New England Journal of Medicine (2011)

Asthma is a disease of the airways characterized by variable airflow obstruction, bronchial hyperresponsiveness, and airway inflammation. Asthma is also accompanied by changes to the structure and composition of the airway walls, collectively termed airway remodeling.1 Cardinal features of airway remodeling include increased numbers of mucus-secreting epithelial cells, thickening of the subepithelial collagen layer, and increases in vascularity and smooth-muscle mass around the airways. There is a strong consensus that airway remodeling contributes to the decline in lung function and the development of fixed airway obstruction present in patients with chronic, persistent asthma.2 Evidence indicates that aspects of airway remodeling . . .
A3.30 Plasma level of HSP70 protein is increased in czech patients with idiopathic inflammatory myopathy
Authors: Tana Svitalkova, Martina Remakova, Lenka Plestilova, Martin Klein, Herman Mann, Jiri Vencovsky, Peter Novota
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Heat shock protein 70 (HSP70) plays an essential role as molecular chaperone by assisting the correct folding of nascent and stress-accumulated misfolded proteins, and preventing their aggregation. These proteins have a dual function depending on their intracellular or extracellular location. Intracellular HSP70 proteins have a protective, antiapoptotic role. Under normal conditions they act as molecular chaperones. Under a stress conditions, the expression of HSP70 genes is induced, which helps the cell to survive otherwise lethal condition. This is due to its important role in apoptosis. The extracellular HSP70 proteins, on the other hand, can act as mediators of immune response. They can elicit an immune response modulated either by the adaptive or innate immune system. Mechanisms of extracellular and intracellular action of Hsp70 is expected to be involved also in autoimmunity development. The aim of this study was to establish the plasma level of Hsp70 protein in patients suffering from IIM and find its possible relation to the clinical features of our patients. <h3>Materials and Methods</h3> We quantified plasma Hsp70 levels in a healthy control group (<i>n</i> = 37) and a group of 34 patient with IIM. Plasma Hsp70 protein was analysed in duplicates using a commercially available high-sensitivity sandwich enzyme-linked immunosorbent assay (ELISA), suitable for detection of Hsp70 protein in serum or plasma samples (Assay Designs EKS-715, USA). Statistical differences between the patients and control groups were established using Mann-Whitney U test. All the expression data are presented as medians with range. <h3>Results</h3> We have found that plasma levels of Hsp70 were significantly higher in patients with myositis than in healthy controls (0.173 [0.000 – 7.647] vs. 0.000 [0.000 – 1.008] ng/ml; p&lt;0.01). However, plasma Hsp70 levels did not correlate with age, CRP, disease activity index (MYOACT), or other clinical features (muscle activity) of our patients. <h3>Conclusions</h3> In this study, we have found that the amount of Hsp70 protein in plasma is significantly higher in IIM patients when compared with healthy controls. Our results correlate with our former findings showing that mRNA levels of HSP70 genes were increased in myositis patients. Finally we can assume that the Hsp70 protein is possibly involved in the pathological mechanism of the myositis. <h3>Acknowledgement</h3> This study was supported by the Internal Grant Agency of the Ministry of Health in the Czech Republic [MZČR NT 13699].
S88 High Sensitivity ERK and AKT Phosphostatus Assays in Lung Cancer and Emphysema
Authors: PAJ Crosbie, EJ Crosbie, M Aspinall-O’Dea, A Pierce, R Shah, R Booton, AW Whetton
Journal: Thorax (2012)

<h3>Introduction</h3> Aberrant expression of oncogenic signalling proteins and their activation by phosphorylation is a key feature of malignancy. Current methodologies do not allow detailed analysis of the phosphorylation patterns of oncoproteins in small clinical samples. Therefore we developed an exquisitely sensitive capillary is oelectric focusing immunoassay (cIEF) method for discriminating phosphorylated isoforms of ERK and AKT in lung tissue. <h3>Methods</h3> Participants undergoing curative resection for early stage NSCLC were recruited. Samples from normal lung and tumour tissue were taken shortly after resection and analysed using cIEF. <h3>Results</h3> Twenty patients were recruited (12 male, 8 female), mean age 67.3 years (SD 7.5), 10 current and 10 former smokers with a mean smoking exposure of 48.4 pack years (SD 24.4). Tumour tissue (9 squamous and 11 adenocarcinoma) was collected and paired macroscopically normal lung that was histologically normal (n=7) or showed emphysema (n=13), graded pathologically as mild (n=7), moderate (n=3) or severe (n=3). The coefficient of variance was 7.6% for ERK and 4.2% for the AKT assay. The limits of detection and quantification were 8ng and 16ng of total protein respectively. Diphosphorylated ERK (active form) was nearly three-fold higher in emphysematous lung tissue than normal lung tissue (p=0.002) and was associated with pathological severity of emphysema. In contrast, diphosphorylated ERK did not differ between paired normal lung and tumour (p=0.45) and there was no correlation of ERK status with age, gender, smoking status, tumour site, histology or stage. AKT was significantly more phosphorylated in tumour than matched normal lung. There was a trend for more phosphorylated AKT with poor differentiation but no correlation with tumour histology, size, site or stage of disease. Current smokers had more phosphorylated AKT than ex-smokers. There was no difference in the phosphorylation patterns of AKT according to age, gender or emphysema status. <h3>Conclusions</h3> We found a strong relationship between diphosphorylated ERK and emphysema. By contrast, AKT phosphostatus was associated with lung cancer but not with emphysema. The requirement for just nanograms of protein defines the potential of this technique for determining the phosphostatus of oncogenic signalling proteins in tiny clinical samples.
ADMINISTRACIÓN TÓPICA DE MITOMICINA C ASOCIADA A DILATACIÓN NEUMÁTICA EN EL TRATAMIENTO DE LAS ESTENOSIS DE ANASTOMOSIS COLORRECTALES
Authors: J Egea, F Alberca, FJ Álvarez, A Pereñiguez, E Estrella, A Serrano, M Alajarin, A Ono, F Carballo
Journal: Endoscopy (2014)

Introducción: las estenosis de anastomosis colorrectales son una complicación relativamente frecuente de esta cirugía. En muchos casos se trata de pacientes asintomáticos, pero en otros estas estenosis son significativas y condicionan una clínica de oclusión/suboclusión intestinal. En esta situación se ha extendido el tratamiento endoscópico con dilataciones neumáticas como primera opción, pero en un porcentaje de pacientes no son efectivas o se precisa de un número muy alto de ellas para conseguir resolver la estenosis.
Uterine Myoma Identified on a Tc-99m MAG3 Scan of a Renal Transplant
Authors: Yiyan Liu, Theresa Park, K. J. Chun, Leonard M. Freeman
Journal: Clinical Nuclear Medicine (2002)

LIU, YIYAN M.D.; PARK, THERESA M.D.; CHUN, K. J. M.D.; FREEMAN, LEONARD M. M.D. Author Information
Effect of Oral Administration of &lt;italic&gt;N,N&lt;/italic&gt;′-2,7-Fluorenylenebisacetamide Combined With Traumatic Ulcers of the Glandular Stomach of Buffalo Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: T Nagayo
Journal: JNCI Journal of the National Cancer Institute (1965)

Male weanling rats of the Buffalo strain were castrated prior to continuous feeding of a diet containing 0.025 percent of N,N′-2,7-fluorenylenebisacctamide. In addition to the castration, one group was also subcutaneously implanted with diethylstilbestrol pellets. Traumatic ulcers of the glandular stomach were produced in the other castrated animals at intervals of 1, 3, 5, and 7 months after the carcinogenic diet was started. Only one carcinoma of the glandular stomach was induced in a castrated rat that received a traumatic ulcer 1 and 7 months after the carcinogenic diet was begun, Two adenocarcinomas developing at the gastroduodenal junction may have originated either from Brunner's glands or from duodenal mucosa. All the castrated animals treated with estrogen that survived 6 months or longer had mammary carcinomas. Incidence of liver tumors in this group was similar to that in the other castrated groups. Castrated rats subjected to traumatic ulcer 3 months after the carcinogenic diet was started had less liver cancer than the noncastrated group. However, traumatic ulceration of the stomach had no effect on the development of cancer of the glandular stomach.
Erlotinib-Induced Cutaneous Toxicity
Authors: Kunal Kumar, Harmandeep Singh, Ravi Kant Gupta, Chandrasekhar Bal, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2014)

Erlotinib is a reversible epidermal growth factor receptor tyrosine kinase inhibitor used to treat advanced non-small cell lung carcinoma patients who have shown progression on at least 1 prior chemotherapy regimen. Most of the patients on erlotinib show cutaneous adverse effects. We report the 18F-FDG PET/CT findings in a case of metastatic non-small cell lung carcinoma on erlotinib chemotherapy with developed skin toxicity.
Abstract 4748: Molecular targets of quinolinone derivatives with anticancer activity
Authors: Gabriela Rylova, Petr Dzubak, Anna Janostakova, Ivo Frydrych, Petr Konecny, Dusan Holub, Tomas Ozdian, Dalibor Dolezal, Miroslav Soural, Jan Hlavac, Marian Hajduch
Journal: Cancer Research (2012)

Abstract Currently, we are testing chemical libraries of quinolinone derivatives, compounds with high selective cytotoxic activity. These compounds, derived from quinolone antibiotics, are well known for their antibacterial, antiprotozoal, cytotoxic and immunosuppressive effects. 2-phenyl-3-hydroxy-4(1H)-quinolinones were tested by MTT assay for cytotoxic activity and some of them proved IC50 values in sub-micromolar concentrations. Cell cycle and DNA/RNA synthesis were further analysed by flow cytometry. The accumulation of cells was observed predominantly in G1 phase together with significant DNA and RNA synthesis inhibition. The most active derivative was tested in in vivo cancer mice model with using hollow fibres. Hollow fibres were filled by leukemic CEM cell line and were implanted subcutaneously and intraperitoneally to mice. Afterwards, mice were treated by tested compound. Hollow fibres were after 14 days taken from mice and surviving cells were tested by cytotoxic MTT assay. activity of tested quinolinone was comparable to doxorubicin. For protein targets identification, we have synthesized biotinylated molecules of original derivatives. Biotinylated derivatives were immobilized on the surface of streptavidin coated magnetic beads and whole complex (magnetic bead-streptavidin-biotin-quinolinone) was incubated with total cellular lysate of the CEM cell line. Thereafter non-bonded proteins were washed-out and specifically bonded proteins were separated on SDS-PAGE gel. Following silver-staining of the gel we identified sample lines with specifically bonded proteins to biotinylated compound and negative control. Specific proteins were cut off from the gel and trypsinized to get peptides for protein identification by MS analysis (LC-MS/MS and LC-MALDI). Identified targets are proteins associated with translational regulation, glucose metabolism and cytoskeleton. Potential targets were validated by western blot and by other assays (reporter cell models, kinase and enzymatic assays, evaluation in vitro transcription and translation). The work was supported by grants: LC07017, CZ.1.07/2.3.00/20.0009 coming from European Social Fund. Infrastructural part of this project (Institute of Molecular and Translational Medicine) was supported from the Operational Programme Research and Development for Innovations (project CZ.1.05/2.1.00/01.0030). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4748. doi:1538-7445.AM2012-4748
Abstract 1931: Impact of bortezomib-induced proteasome inhibition <i>in vivo</i> on antitumor T cell responses
Authors: Anil Shanker, Rachel De Kluyver, Thomas J. Sayers
Journal: Cancer Research (2010)

Abstract Inhibition of cellular proteasome function crucial for protein turn-over is a recent approach to overcome the resistance of tumors to cell death, a major clinical problem. Bortezomib (also known as Velcade/PS-341), a specific and reversible proteasome inhibitor, has been shown to sensitize some mouse and human tumors to apoptosis induced by the TNF-related apoptosis-inducing ligand (TRAIL) or its receptor (DR5) agonist monoclonal antibody (mAb). In established mouse renal cell (Renca) and breast (4T1) tumor models, the administration of DR5 agonist mAb to tumor-bearing mice pre-treated with bortezomib reduced experimental lung metastases. The combination of bortezomib and DR5 agonist mAb also significantly increased long-term survival of mice bearing Renca tumors compared with either agent alone. The therapeutic effects of bortezomib on tumor metastases and survival of tumor-bearing mice occurred in the absence of overt toxicity. However, little is known concerning the effects of bortezomib on specific immune responses. We thus analyzed the effects of proteasome inhibition on anti-tumor T cell responses in vivo. In mice with established Renca-HA tumor expressing influenza virus hemagglutinin (HA) as a surrogate tumor antigen, we evaluated the antigen-specific proliferation of adoptively transferred monoclonal HA-specific MHC class I or II restricted T cells following various schedules of bortezomib administration. No inhibition of T cell proliferation or cytolytic function in vivo was observed following bortezomib treatments. Nor was there any evidence of defective dendritic cell maturation in bortezomib-treated mice. However, a significant decrease in total T cell yield was noted in the tumor-draining LNs of mice treated with bortezomib. Thus, bortezomib-inhibitory effects on T cell responses seem quantitative rather than qualitative. The basis for this decrease in T cell number is under further investigation. The findings imply that, with an appropriate scheduling, it may be possible to combine bortezomib-induced sensitization of tumors to apoptosis with tumor-specific T cell immunotherapy regimens for increased therapeutic benefit in cancer. Funded in part by NCI Contract # N01-CO-12400 and HHSN261200800001E. 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 1931.
Effect of Levamisole on E-Rosette-Forming Cells in Vivo and in Vitro in Hodgkin's Disease
Authors: B. Ramot, M. Biniaminov, Ch. Shoham, E. Rosenthal
Journal: New England Journal of Medicine (1976)

Incubation in vitro of lymphocytes from patients with Hodgkin's disease with 40 μg per milliliter of levamisole resulted in a rise in the number of E-rosette-forming cells from 33.6 ± 12.5 per cent (mean ± S.D.) to 56.7 ± 14.6 per cent. The drug had no effect on normal lymphocytes. Ten patients with Hodgkin's disease treated six months previously with levamisole were restudied. The positive skin tests to PPD, candida and mumps persisted. However, the E-rosette-forming cells decreased to the pretreatment levels (34.7 ± 6.4 per cent). Readministration of 150 mg of levamisole for three days raised the number of E-rosette-forming cells to 54.1 ± 5.6 per cent. This effect was observed for at least two months. However, the drug had no effect in vitro as long as the in vivo effect persisted. These results demonstrate a clear immunologic effect of levamisole in Hodgkin's disease and indicate that the low number of E-rosette-forming cells is not due to a real T-cell depletion. (N Engl J Med 294:809–811, 1976)
Increased Nerve-Growth-Factor β-Chain Cross-Reacting Material in Familial Dysautonomia
Authors: David C. Siggers, John G. Rogers, Samuel H. Boyer, Louise Margolet, Henry Dorkin, Shailesh P. Banerjee, Eric M. Shooter
Journal: New England Journal of Medicine (1976)

To determine whether dysautonomia arises from alteration in nerve-growth factor (NGF), we measured serum levels of NGF subunits in normal and dysautonomic subjects using a biologic assay based on neurite outgrowth from chick ganglions, a binding assay based on displacement of radiolabeled betaNGF from rabbit-ganglion microsomes, and radioimmunoassays of chi, gamma and betaNGF subunits via antiserum to mouse NGF polypeptides. A threefold increase (P less than 0.001) in serum antigen levels of the biologically active subunit (betaNGF) was found for dysautonomic as compared with normal subjects. By all other assays, the groups were alike. The marked discrepancy in betaNGF levels between antigenic and functional (biologic and binding) measurements suggests a qualitative abnormaltiy of betaNGF in dysautonomia. Alternatively, elevation of betaNGF antigen can be regarded as secondary to disease. This alternative seems less likely since we must then suppose that the normalcy of functional assays in spurious.
Radiation-Induced Osteosarcoma Might Mimic Metastatic Bone Lesions
Authors: Masamichi Koyama, Mitsuru Koizumi, Kenji Umayahara, Nobuhiro Takeshima, Shunji Takahashi
Journal: Clinical Nuclear Medicine (2015)

We report on a 53-year-old woman with osteosarcoma of the skull who underwent radiation therapy for metastatic brain tumor. She had a history of uterine endometrial cancer treated with chemotherapy and surgery 9 years previously. FDG PET/CT for surveillance showed nodular accumulation at the right suprainguinal region and very avid accumulation at the left side of the occipital bone. Bone scan showed increased accumulation at the same portion of the occipital bone. The occipital tumor was surgically removed and diagnosed as radiation-induced osteosarcoma.