tbuckley/cabot-search huggingface dataset:
Contamination of Health Care Personnel During Removal of Personal Protective Equipment
Authors: Myreen E. Tomas, Sirisha Kundrapu, Priyaleela Thota, Venkata C. K. Sunkesula, Jennifer L. Cadnum, Thriveen Sankar Chittoor Mana, Annette Jencson, Marguerite O’Donnell, Trina F. Zabarsky, Michelle T. Hecker, Amy J. Ray, Brigid M. Wilson, Curtis J. Donskey
Journal: JAMA Internal Medicine (2015)

<h3>Importance</h3> Contamination of the skin and clothing of health care personnel during removal of personal protective equipment (PPE) contributes to dissemination of pathogens and places personnel at risk for infection. <h3>Objectives</h3> To determine the frequency and sites of contamination on the skin and clothing of personnel during PPE removal and to evaluate the effect of an intervention on the frequency of contamination. <h3>Design, Setting, and Participants</h3> We conducted a point-prevalence study and quasi-experimental intervention from October 28, 2014, through March 31, 2015. Data analysis began November 17, 2014, and ended April 21, 2015. Participants included a convenience sample of health care personnel from 4 Northeast Ohio hospitals who conducted simulations of contaminated PPE removal using fluorescent lotion and a cohort of health care personnel from 7 study units in 1 medical center that participated in a quasi-experimental intervention that included education and practice in removal of contaminated PPE with immediate visual feedback based on fluorescent lotion contamination of skin and clothing. <h3>Main Outcomes and Measures</h3> The primary outcomes were the frequency and sites of contamination on skin and clothing of personnel after removal of contaminated gloves or gowns at baseline vs after the intervention. A secondary end point focused on the correlation between contamination of skin with fluorescent lotion and bacteriophage MS2, a nonpathogenic, nonenveloped virus. <h3>Results</h3> Of 435 glove and gown removal simulations, contamination of skin or clothing with fluorescent lotion occurred in 200 (46.0%), with a similar frequency of contamination among the 4 hospitals (range, 42.5%-50.3%). Contamination occurred more frequently during removal of contaminated gloves than gowns (52.9% vs 37.8%,<i>P</i> = .002) and when lapses in technique were observed vs not observed (70.3% vs 30.0%,<i>P</i> &lt; .001). The intervention resulted in a reduction in skin and clothing contamination during glove and gown removal (60.0% before the intervention vs 18.9% after,<i>P</i> &lt; .001) that was sustained after 1 and 3 months (12.0% at both time points,<i>P</i> &lt; .001 compared with before the intervention). During simulations of contaminated glove removal, the frequency of skin contamination was similar with fluorescent lotion and bacteriophage MS2 (58.0% vs 52.0%,<i>P</i> = .45). <h3>Conclusions and Relevance</h3> Contamination of the skin and clothing of health care personnel occurs frequently during removal of contaminated gloves or gowns. Educational interventions that include practice with immediate visual feedback on skin and clothing contamination can significantly reduce the risk of contamination during removal of PPE.
Proteomics studies confirm the presence of alternative protein isoforms on a large scale
Authors: Michael L. Tress, Bernd Bodenmiller, Rudolf Aebersold, Alfonos Valencia
Journal: Genome biology (2008)

Alternative splicing of messenger RNA permits the formation of a wide range of mature RNA transcripts and has the potential to generate a diverse spectrum of functional proteins. Although there is extensive evidence for large scale alternative splicing at the transcript level, there have been no comparable studies demonstrating the existence of alternatively spliced protein isoforms.Recent advances in proteomics technology have allowed us to carry out a comprehensive identification of protein isoforms in Drosophila. The analysis of this proteomic data confirmed the presence of multiple alternative gene products for over a hundred Drosophila genes.We demonstrate that proteomics techniques can detect the expression of stable alternative splice isoforms on a genome-wide scale. Many of these alternative isoforms are likely to have regions that are disordered in solution, and specific proteomics methodologies may be required to identify these peptides.
Synovial fluid chondroitin and keratan sulphate epitopes, glycosaminoglycans, and hyaluronan in arthritic and normal knees
Authors: C. Belcher, R. Yaqub, F. Fawthrop, M. Bayliss, M. Doherty
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVES</h3> To determine concentrations of chondroitin sulphate (CS) and keratan sulphate (KS) epitopes, glycosaminoglycans (GAGs) and hyaluronan (HA) in knee synovial fluid (SF) from normal subjects and patients with osteoarthritis (OA) or rheumatoid arthritis (RA), to test whether these variables may be used as markers of the OA process. <h3>METHODS</h3> OA was subdivided into large joint OA (LJOA), nodal generalised OA (NGOA), and OA with calcium pyrophosphate crystal deposition (CPA). Clinical assessment of inflammation (0-6) was undertaken on OA and RA knees. Knee SF was examined by enzyme linked immunosorbent assay for: CS epitopes, using monoclonal antibodies 3-B-3 and 7-D-4; KS epitope using monoclonal antibody 5-D-4; and HA, using biotinylated HA binding region of cartilage proteoglycan. Total sulphated GAGs were measured by dye binding with 1:9 dimethylmethylene blue. <h3>RESULTS</h3> Increased SF 3-B-3 concentrations and 3-B-3/GAG ratio were found in OA, compared with RA or normal knees, with higher 3-B-3 and 3-B-3/GAG in LJOA and NGOA than in CPA. SF 7-D-4 and 7-D-4/GAG were reduced in RA, compared with normal and OA; SF 5-D-4 was reduced in OA compared with normal. GAG and HA concentrations were decreased in both OA and RA. No correlations with radiographic scores were observed, but SF 7-D-4 was lower in 'inflamed' compared with 'non-inflamed' RA and OA knees. In patients with bilateral samples there were strong correlations between right and left knees for all SF variables. <h3>CONCLUSIONS</h3> Changed concentrations of SF CS and KS can be detected in OA with a profile that differs from that seen in RA. Clinical subgrouping and local joint inflammation may influence these measures, supporting different pathogenesis within OA subgroups and requirement for careful patient characterisation in SF studies.
Neutrophils in cystic fibrosis
Authors: D G Downey, S C Bell, J S Elborn
Journal: Thorax (2008)

Lung injury in cystic fibrosis is caused by recurrent airway infection and inflammation. Neutrophils are important in combating these infections but are also the predominate cells involved in the inflammatory process. This review of neutrophils in cystic fibrosis describes the cellular mechanisms involved in their migration into the airways and their role in bacterial phagocytosis. We discuss the inflammatory process and its resolution and ultimately how neutrophil function can be modulated.
γδ T Cells Provide an Early Source of Interferon γ in Tumor Immunity
Authors: Yunfei Gao, Wancai Yang, Meng Pan, Eileen Scully, Michael Girardi, Leonard H. Augenlicht, Joe Craft, Zhinan Yin
Journal: The Journal of Experimental Medicine (2003)

Interferon (IFN)-γ is necessary for tumor immunity, however, its initial cellular source is unknown. Because γδ T cells primarily produce this cytokine upon activation, we hypothesized that they would provide an important early source of IFN-γ in tumor immunosurveillance. To address this hypothesis, we first demonstrated that γδ T cell–deficient mice had a significantly higher incidence of tumor development after challenge with a chemical carcinogen methylcholanthrene (MCA) or inoculation with the melanoma cell line B16. In wild-type mice, γδ T cells were recruited to the site of tumor as early as day 3 after inoculation, followed by αβ T cells at day 5. We then used bone marrow chimeras and fetal liver reconstitutions to create mice with an intact γδ T cell repertoire but one that was specifically deficient in the capacity to produce IFN-γ. Such mice had a higher incidence of tumor development, induced either with MCA or by inoculation of B16 melanoma cells, compared with mice with IFN-γ–competent γδ T cells. Moreover, genetic deficiency of γδ T cells resulted in impaired IFN-γ production by tumor antigen-triggered αβ T cell upon immunization with tumor lysate. These results demonstrate that γδ T cells can play a necessary role in tumor immunity through provision of an early source of IFN-γ that in turn may regulate the function of tumor-triggered αβ T cells.
Abnormal Postexercise Cardiovascular Recovery and Its Determinants in Patients After Right Ventricular Outflow Tract Reconstruction
Authors: Hideo Ohuchi, Hiroyuki Ohashi, Jiksoo Park, Johji Hayashi, Aya Miyazaki, Shigeyuki Echigo
Journal: Circulation (2002)

Abnormal responses of heart rate (HR) and oxygen uptake (VO2) during exercise characterize patients after right ventricular outflow tract reconstruction (RVOTR) for congenital heart defects. However, little is known about the postexercise dynamics.We evaluated postexercise cardiovascular dynamics in 52 patients after closure of an atrioventricular septal defect (group A), 79 patients after RVOTR (group B), and 44 control subjects. HR variability, arterial baroreflex sensitivity (BRS), plasma norepinephrine, and hemodynamics were measured. Although there was no difference between group A and control subjects, declines in HR and VO2 after light and peak exercise and in systolic blood pressure (SBP) after peak exercise were delayed in group B. Age, low-frequency component of HR variability, and plasma norepinephrine were independent determinants of early HR decline. Peak SBP and VO2 had a great impact on the corresponding recoveries. When the peak values were excluded, body weight, BRS, and right ventricular ejection fraction were independent determinants of early SBP decline. BRS and the pulmonary artery resistance were independent determinants of VO2 decline throughout recovery, and age and right systolic ventricular pressure also determined the early VO2 decline. BRS and low-frequency component of HR variability were determined independently by the number of surgical procedures.In RVOTR patients, in addition to metabolic and autonomic maturation, surgery-related abnormal cardiac autonomic nervous activity and impaired hemodynamics have a great impact on delayed postexercise cardiovascular recovery.
Occlusion of Lumina in Small Arterioles During Vasoconstriction
Authors: Robert L. Van Citters
Journal: Circulation Research (1966)

The microscopic appearance of small arterioles during epinephrine-induced vasoconstriction was studied in the dog mesentery. The tissues were quick-frozen in situ with liquid isopentane, freeze-substituted, and sectioned serially. Obliteration of the lumina of small arterioles during vasoconstriction was demonstrated in both random and serial sections. Endothelial cells, which were ordinarily flattened against the internal elastic membrane, were compressed and deformed during vasoconstriction, so that they protruded into the lumen and often coalesced in the center of the vessel to form a mechanical obstruction to blood flow. Vascular obliteration occurred commonly in very small arterioles, but was observed with diminishing frequency in progressively larger arterioles, and was not identified in vessels large enough to accommodate more than 10 endothelial cells in cross sections. In an ideal cylinder, tension is greatest at the innermost layer, and the gradient of tension across the wall falls off in a nonlinear fashion. These conditions probably do not hold in a functioning arteriole.
Pretreatment with Cisplatin Enhances E7-Specific CD8+ T-Cell–Mediated Antitumor Immunity Induced by DNA Vaccination
Authors: Chih-Wen Tseng, Chien-Fu Hung, Ronald D. Alvarez, Cornelia Trimble, Warner K. Huh, Daejin Kim, Chi-Mu Chuang, Cheng-Tao Lin, Ya-Chea Tsai, Liangmei He, Archana Monie, T-C. Wu
Journal: Clinical Cancer Research (2008)

Because the combination of multiple modalities for cancer treatment is more likely to generate more potent therapeutic effects for the control of cancer, we have explored the combination of chemotherapy using cisplatin, which is routinely used in chemotherapy for advanced cervical cancer, with immunotherapy using DNA vaccines encoding calreticulin (CRT) linked to human papillomavirus type 16 E7 antigen (CRT/E7) in a preclinical model.We characterized the combination of cisplatin with CRT/E7 DNA vaccine using different regimen for its potential ability to generate E7-specific CD8+ T-cell immune responses as well as antitumor effects against E7-expressing tumors.Our results indicate that treatment of tumor-bearing mice with chemoimmunotherapy combining cisplatin followed by CRT/E7 DNA generated the highest E7-specific CD8+ T-cell immune response and produced the greatest antitumor effects and long-term survival as well as significant levels of E7-specific tumor-infiltrating lymphocytes compared with all the other treatment regimens. Furthermore, we found that treatment with cisplatin leads to the cell-mediated lysis of E7-expressing tumor cells in vitro and increased number of E7-specific CD8+ T-cell precursors in tumor-bearing mice. In addition, we observed that E7-specific CD8+ T cells migrate to and proliferate in the location of TC-1 tumors in mice treated with cisplatin.Thus, our data suggest that chemoimmunotherapy using cisplatin followed by CRT/E7 DNA vaccine is an effective treatment against E7-expressing tumors and may potentially be translated into the clinical arena.
Intraoperative Avidination for Radionuclide Therapy: A Prospective New Development to Accelerate Radiotherapy in Breast Cancer
Authors: Giovanni Paganelli, Mahila Ferrari, Laura Ravasi, Marta Cremonesi, Concetta De Cicco, Viviana Galimberti, Gregory Sivolapenko, Alberto Luini, Rita De Santis, Laura Lavinia Travaini, Maurizio Fiorenza, Marco Chinol, Stefano Papi, Claudio Zanna, Paolo Carminati, Umberto Veronesi
Journal: Clinical Cancer Research (2007)

Abstract Purpose: In a continuous effort to seek for anticancer treatments with minimal side effects, we aim at proving the feasibility of the Intraoperative Avidination for Radionuclide Therapy, a new procedure for partial breast irradiation. Experimental Design: To assess doses of 90Y-DOTA-biotin to target (i.e., breast tumor bed) and nontarget organs, we did simulation studies with 111In-DOTA-biotin in 10 candidates for conservative breast surgery. Immediately after quadrantectomy, patients were injected with 100-mg avidin in the tumor bed. On the following day, patients were given 111In-DOTA-biotin (∼111 MBq) i.v. after appropriate chase of biotinylated albumin (20 mg) to remove circulating avidin. Biokinetic studies were done by measuring radioactivity in scheduled blood samples, 48-h urine collection, and through scintigraphic images. The medical internal radiation dose formalism (OLINDA code) enabled dosimetry assessment in target and nontarget organs. Results: Images showed early and long-lasting radioactive biotin uptake in the operated breast. Rapid blood clearance (&amp;lt;1% at 12 h) and urine excretion (&amp;gt;75% at 24 h) were observed. Absorbed doses, expressed as mean ± SD in Gy/GBq, were as low as 0.15 ± 0.05 in lungs, 0.10 ± 0.02 in heart, 0.06 ± 0.02 in red marrow, 1.30 ± 0.50 in kidneys, 1.50 ± 0.30 in urinary bladder, and 0.06 ± 0.02 in total body, whereas in the targeted area, they increased to 5.5 ± 1.1 Gy/GBq (50% ISOROI) and 4.8 ± 1.0 Gy/GBq (30% ISOROI). Conclusion: Our preliminary results suggest that Intraoperative Avidination for Radionuclide Therapy is a simple and feasible procedure that may improve breast cancer patients' postsurgical management by shortening radiotherapy duration.
The T-cell Receptor Repertoire of Tumor-Infiltrating Regulatory T Lymphocytes Is Skewed Toward Public Sequences
Authors: Alexander Sainz-Perez, Annick Lim, Brigitte Lemercier, Claude Leclerc
Journal: Cancer Research (2012)

Abstract The accumulation of CD4+ T regulatory cells (Treg) in tumor tissue is a widely described phenomenon in mouse models and in human cancer patients. Understanding the mechanisms by which Treg migrate and accumulate in tumors is important because they strongly influence the potential efficacy of many immunotherapies. In this study, we used immunoscope technology to analyze the T-cell receptor (TCR) repertoire of tumor-infiltrating T cells in non-TCR transgenic mice. Both tumor-infiltrating Tregs and T effector cells (Teff) displayed sequence profiles in the CDR3 region that were characteristic of biased repertoires seen during clonal cell expansions, implying that strong T-cell responses have occurred within the tumor tissue. By comparing the TCR sequences of tumor-infiltrating Tregs, we obtained evidence of the presence of so-called public TCR sequences that are common to many individuals yet were tumor-specific in nature. Such comparisons also suggested that the Treg–Teff conversion process is not an active process at the tumor site or tumor-draining lymph nodes. Our findings strongly suggest that Treg infiltration of tumor tissue is followed by marked proliferation of a few dominant T-cell clones in the tumor. Cancer Res; 72(14); 3557–69. ©2012 AACR.
An unusual cause of weight loss in a young Caucasian man
Authors: Paolo Cecinato, Lorenzo Fuccio, Elena Sabattini, Liboria Laterza, Alessandra Caponi, Francesco Azzaroli, Giuseppe Mazzella
Journal: Gut (2013)

A 37-year-old Caucasian male presented to our institution for progressive weight loss and recurrent abdominal pain. An enteral CT performed in another centre showed a diffuse thickening of the duodenal walls suggestive of lymphoma or Crohn’s disease.

Esophagogastroduodenoscopy showed a normal appearance of gastroesophageal mucosa while the duodenal and proximal jejunal mucosa appeared completely covered with pseudo-polypoid lesions with maximum size of 5 mm (figure 1A,B). At the ileocolonoscopy, the colorectal mucosa was diffusely micronodular (figure 1D), while the terminal ileum presented same lesions detected in the duodenum (figure 1C).



Figure 1 
Endoscopic view: (A) duodenum, (B) jejunum, (C) ileum, (D) colon.



Enteroscopy confirmed the presence of pseudopolypoid lesions also in the jejunum and ileum, …
Left ventricular regional relaxation and its nonuniformity in hypertrophic nonobstructive cardiomyopathy.
Authors: W Hayashida, T Kumada, F Kohno, M Noda, N Ishikawa, J Kojima, Y Himura, C Kawai
Journal: Circulation (1991)

Regional nonuniformity has been suggested to be closely related to left ventricular (LV) relaxation in diseased heart. The purpose of the present study was to assess LV global and regional relaxation in patients with nonobstructive hypertrophic cardiomyopathy (HCM).Left ventriculography was conducted simultaneously with pressure micromanometry in 10 normal control subjects and 11 patients with nonobstructive HCM. LV silhouettes in the right anterior oblique projection were divided into eight regions, and regional wall stress during isovolumic relaxation was computed for six regions from the midventricle to the apex. In HCM patients, isovolumic relaxation time (IRT) and the time constant of LV pressure decrease (Tp) were greater than in control subjects (IRT, 84 +/- 13 versus 66 +/- 6 msec; Tp, 51 +/- 8 versus 36 +/- 5 msec, respectively; p less than 0.01). In HCM patients, the (-)dP/dt upstroke pattern was convex-downward, and dP/dt(20/60), the ratio of dP/dt values 20 and 60 msec after peak (-)dP/dt, was less than in control subjects (1.46 +/- 0.16 versus 2.15 +/- 0.14, p less than 0.01). These findings suggest that there is impaired LV relaxation in HCM patients. End-systolic regional wall stress was lower, and the time constant of regional stress decrease (Tst) was prolonged for each region in HCM patients compared with control subjects. In the HCM group, Tst tended to be more prolonged in regions with increased wall thickness than in regions with normal wall thickness (60 +/- 15 versus 50 +/- 11 msec, p less than 0.01). The coefficient of variation for Tst values in six areas of the left ventricle was calculated in each subject and was greater in HCM patients than in control subjects (13 +/- 7% versus 7 +/- 3%, p less than 0.05), indicating regional nonuniformity in Tst during isovolumic relaxation in HCM patients.Significant correlations existed between the coefficients of variation for Tst and Tp (r = 0.80, p less than 0.01), IRT (r = 0.79, p less than 0.01), and dP/dt(20/60) (r = -0.67, p less than 0.05) in the HCM group. Thus, regional nonuniformity is closely related to the impairment of LV relaxation in HCM.
THE FIRST COMPONENT OF THE KININ-FORMING SYSTEM IN HUMAN AND RABBIT PLASMA
Authors: C. G. Cochrane, K. D. Wuepper
Journal: The Journal of Experimental Medicine (1971)

The isolation and characterization of the first component of the kinin-forming system in human and rabbit plasma are presented. Functionally, the molecule is the precursor of the activator of prekallikrein (Pre-PKA) and evidence is presented that it is identical with Hageman factor (clotting factor XII). The component from each plasma possessed similar characteristics. This molecule was found to have a mol wt of 110,000 and sedimentation rate of 4.6S. It migrated in electrophoresis as a ß-globulin, having an isoelectric point of 6.1. Upon activation with glass, kaolin, diatomaceous earth, ellagic acid, or trypsin, the activated molecule converted purified prekallikrein (prokininogenase) to the active enzyme. Clot-promoting activity was associated with the capacity to activate prekallikrein through each procedure of isolation. The clot-promoting factor was in precursor form, requiring treatment with kaolin or trypsin to gain activity. Evidence indicated that the protein was Hageman factor (factor XII): it promoted clotting of factor XII-deficient, but not Factor XI- or IX-deficient plasma, and did not convert fibrinogen to fibrin it bound to and was activated by kaolin or other negatively charged particles in the presence of chelating agents; the activation by kaolin could be prevented by pretreating the kaolin with hexadimethrine bromide (H Br); prekallikrein-activating and clot-promoting activities were identical in their physical properties; and the prekallikrein activator could not be detected in Hageman factor-deficient plasma. Activation of Hageman factor was accompanied by cleavage of the molecule into several fragments, one of which possessed prekallikrein-activating (PKA) and clot-promoting properties. The PKA fragment sedimented at 2.6S and by gel filtration was found to have a molecular weight of 32,000. The PKA possessed only 1/50 the clot-promoting capacity of the freshly activated native molecule.