tbuckley/cabot-search huggingface dataset:
T-cell receptor–HLA-DRB1 associations suggest specific antigens in pulmonary sarcoidosis
Authors: Johan Grunewald, Ylva Kaiser, Mahyar Ostadkarampour, Natalia V. Rivera, Francesco Vezzi, Britta Lötstedt, Remi-André Olsen, Lina Sylwan, Sverker Lundin, Max Käller, Tatiana Sandalova, Kerstin M. Ahlgren, Jan Wahlström, Adnane Achour, Marcus Ronninger, Anders Eklund
Journal: European Respiratory Journal (2015)

In pulmonary sarcoidosis, CD4 + T-cells expressing T-cell receptor Vα2.3 accumulate in the lungs of HLA-DRB1*03 + patients. To investigate T-cell receptor-HLA-DRB1*03 interactions underlying recognition of hitherto unknown antigens, we performed detailed analyses of T-cell receptor expression on bronchoalveolar lavage fluid CD4 + T-cells from sarcoidosis patients. Pulmonary sarcoidosis patients (n=43) underwent bronchoscopy with bronchoalveolar lavage. T-cell receptor α and β chains of CD4 + T-cells were analysed by flow cytometry, DNA-sequenced, and three-dimensional molecular models of T-cell receptor-HLA-DRB1*03 complexes generated. Simultaneous expression of Vα2.3 with the Vβ22 chain was identified in the lungs of all HLA-DRB1*03 + patients. Accumulated Vα2.3/Vβ22-expressing T-cells were highly clonal, with identical or near-identical Vα2.3 chain sequences and inter-patient similarities in Vβ22 chain amino acid distribution. Molecular modelling revealed specific T-cell receptor-HLA-DRB1*03-peptide interactions, with a previously identified, sarcoidosis-associated vimentin peptide, (Vim) 429–443 DSLPLVDTHSKRTLL, matching both the HLA peptide-binding cleft and distinct T-cell receptor features perfectly. We demonstrate, for the first time, the accumulation of large clonal populations of specific Vα2.3/Vβ22 T-cell receptor-expressing CD4 + T-cells in the lungs of HLA-DRB1*03 + sarcoidosis patients. Several distinct contact points between Vα2.3/Vβ22 receptors and HLA-DRB1*03 molecules suggest presentation of prototypic vimentin-derived peptides.
Proliferation of Bile Ductular Cells in the Spontaneously Hypertensive Rat Fed N,N'-2,7-Fluorenylenebisacetamide
Authors: Masao Ito, Kazuo Masuko, Mutsushi Matsuyama, Harumi Suzuki, Takeo Nagayo, Kyuzo Aoki
Journal: JNCI Journal of the National Cancer Institute (1973)

Marked proliferation of the bile ductular cells accompanied by ascites was observed in the liver of spontaneously hypertensive rats (SHR) fed N,N'-2,7-fluorenylenebisacetamide (2,7-FAA) for 1 month. A milder form of the lesions was also seen in normotensive Wistar, Sprague-Dawley, and Buffalo rats fed 2,7-FAA. The proliferation of the ductular cells in SHR reached a peak at the end of the 4th week of 2,7-FAA feeding. The degree of proliferation in SHR was more than 7 times higher than in the other 3 strains. The DNA synthesis of the ductular cells in SHR was markedly increased at the end of the 1st week as compared with the normotensive Wistar. The ductular cell proliferation in SHR was closely related to the age at which the administration of 2,7-FAA was started. When given to rats 10 weeks old, proliferation was prominent and progressed irreversibly. However, it was slight when 2,7-FAA was given at 7 or 15 weeks of age. The administration of 2,7-FAA evidently suppressed hypertension in SHR but did not affect the blood pressure in Wistar rats. These observations suggest that important changes in metabolic pathways occur in the liver of SHR at the initial stage of hypertension and amplify the action of 2,7-FAA.
Quality-of-life (QoL) measures in advanced non-small cell lung cancer (NSCLC) patients and their association with treatment choices across 5 European countries: Preliminary data from the ACTION study
Authors: F. Pimental, A. Szczepura, M. Thomas, B. Frimodt-Moller, M. Belger, J. Watkins, M. Watt
Journal: Journal of Clinical Oncology (2005)

8081 Background: ACTION (Assessment of Cost and ouTcomes of chemotherapy In an Observational setting in patients with advanced NSCLC) is an on-going, pan-European, observational study in routine clinical practice. This report summarizes baseline observer Lung Cancer Symptom Scale (LCSS) and EQ-5D health status scores among countries and according to treatment choice. Methods: Between 4/2003 and 6/2004, 993 patients (pts) were recruited. Pts were ≥18 years old and receiving first-line chemotherapy for IIIB/IV NSCLC. Baseline data were available in 967 pts. Results: Median age was 64 years (range 31–90), 71% were male. WHO PS was 0 in 21%, 1 in 65%, 2 in 10%, and 3/4 in 4%. 35% of patients were stage IIIB. There were 0, 1, 2, 3, 4, or >4 metastatic organs involved in 27%, 47%, 18%, 6%, 2%, and 0.2% of pts, respectively. Surgery and palliative or radical radiotherapy had been performed in 12%, 12%, and 1% of pts, respectively. The mean baseline LCSS, EQ-5D health status and VAS scores were calculated. Conclusions: There are variations in QoL scores between countries and treatment choice; these will be analyzed in-depth as a follow-up. Longitudinal follow-up of this patient cohort will allow a unique investigation of the association between health status and treatment outcomes. The analysis will also stratify by additional variables (eg, age, stage, PS). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly AstraZeneca, Eli Lilly, Pierre Fabre, Roche Eli Lilly AstraZeneca, Aventis, Lilly Oncology, Pierre Fabre
Abstract 11212: Left Atrial Volume Index Predicts Recurrence of Stroke in Patients With Non-Sustained Atrial Tachycardia
Authors: Hyemoon Chung, Pil-Ki Min, Young Won Yoon, Byoung-Kwon Lee, Bum-Kee Hong, Se-Joong Rim, Hyuck Moon Kwon, Eui-Young Choi, Jong-Youn Kim
Journal: Circulation (2014)

Introduction: NSAT is known to appear more frequently in patients with paroxysmal AF. Additionally enlarged LA is considered to be an independent risk factor for newly diagnosed AF. We investigated the relationship between non-sustained atrial tachycardia (NSAT) and stroke recurrence and the risk factors that may predict stroke recurrence in stroke patients where 24-hour Holter monitoring documented NSAT without paroxysmal AF. Hypothesis: We hypothesized that those patients who presented with NSAT and enlarged LA would have a higher incidence of stroke recurrence. Methods: 214 patients (102 males, mean 70±11 years) with acute ischemic stroke and NSAT were subject to 24-hour Holter monitoring. During follow-up patients were assessed for stroke recurrence and echocardiographic parameters. Results: During a mean follow-up period of 36±34 months, the recurrence rate of stroke was 11.8% (25 of 214). Those patients with recurrence had a larger LA diameter (34.73±5.04 vs. 40.64±3.45mm, p&lt;0.001), LA volume index (LAVI, 22.56±5.86vs. 33.81±7.80 ml/m 2 , p&lt;0.001and increased E/E’ (12.27±4.86 vs. 14.49±4.38, p=0.032) compared to patients without recurrence (n=189). A Kaplan-Meier survival rate was significantly lower in patients with enlarged LA size (LAVI&gt;28 mm 3 /m 2 ) compared with patients without enlarged LA size (LAVI≤28 mm 3 /m 2 ) (p&lt;0.001 by log-rank test). Cox regression analysis revealed that left atrial volume index hazard ratio (HR: 1.148, 95% CI: 1.092-1.206, p&lt;0.001) was an independent predictor for stroke recurrence in patients with NSAT. Areas under the Receiver Operating Characteristics (ROC) curve of LAVI for recurrence of stroke was 0.876 (95% CI: 0.791-0.960, p&lt;0.001). Conclusions: In patients with acute ischemic stroke and NSAT, increased LAVI predicts an increased risk of stroke recurrence. This study supports the potential use of anticoagulants in stroke patients with NSAT and increased LAVI without documented AF to reduce recurrent stroke.
Skin Damage in Chronic Venous Insufficiency: Does an Oxygen Diffusion Barrier Really Exist?
Authors: T R Cheatle, G M McMullin, J Farrah, P D Coleridge Smith, J H Scurr
Journal: Journal of the Royal Society of Medicine (1990)

Eleven patients with lipodermatosclerosis (LDS) and 14 patients without venous or arterial disease underwent measurement of xenon-133 (133Xe) half-clearance times from the gaiter region of the leg. Xenon has similar diffusion characteristics to oxygen, and the investigation reflects the ability of the isotope to diffuse from the skin surface into capillary blood. Median skin half-clearance time for skin in the LDS group was 2.2 min and in the control group 2.1 min. From the subcutaneous tissues, the respective times were 14.1 and 17.4 minutes. These differences are not statistically significant. The study fails to yield evidence suggesting that an oxygen diffusion barrier exists in lipodermatosclerosis.
GPs will consider “mass resignation” if government ignores crisis
Authors: Matthew Limb
Journal: BMJ (2016)

GPs have threatened to consider mass resignations from NHS contracts to make sure that the government delivers a “rescue package” for general practice.

The BMA’s General Practitioners Committee will ask GPs’ views about submitting undated resignations if a bailout plan isn’t proposed within six months.

The move was supported by local medical committee (LMC) representatives after a debate at a special BMA conference in London on 30 January.

GPs could also be balloted on the work they would stop doing—to reduce workload and ensure safe and sustainable care—under a motion approved by the conference.

The General Practitioners Committee would also …
Recruitment of Effector T Lymphocytes Against a Tumor Allograft by T Lymphocytes Sensitized In Vitro2
Authors: Abraham J. Treves, Irun R. Cohen
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Recruitment of Effector T Lymphocytes Against a Tumor Allograft by T Lymphocytes Sensitized In Vitro Get access Abraham J. Treves, Abraham J. Treves Search for other works by this author on: Oxford Academic PubMed Google Scholar Irun R. Cohen Irun R. Cohen Department of Cell Biology, The Welzmann Institute of Science, Rehovot, Israel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 6, December 1973, Pages 1919–1925, https://doi.org/10.1093/jnci/51.6.1919 Published: 01 December 1973 Article history Received: 31 May 1973 Accepted: 08 August 1973 Published: 01 December 1973
Dynamic contrast-enhanced Doppler ultrasound (DCE-US) is a useful radiological assessment to early predict the outcome of patients with gastrointestinal stromal tumors (GIST) treated with imatinib (IM)
Authors: M. Lamuraglia, A. Le Cesne, L. Chami, S. Bonvalot, P. Terrier, T. Tursz, A. Roche, N. Lassau
Journal: Journal of Clinical Oncology (2006)

9539 Background: DCE-US combined with perfusion software VRI (Vascular Recognition Imaging) and contrast agent injection (Sonovue-Bracco) is a simple and reproductible imaging technique that allows an early and accurate evaluation of IM activity in GIST patients (Lassau et al, ASCO 2004). The objective of this study was to correlate the results observed with DCE-US with the outcome of c-Kit-positive GIST pts treated with IM and to early detect secondary resistance to IM. Methods: 36 pts with advanced GIST were prospectively included in a monocentric imaging trial. DCE-US was performed before IM administration (d0) on days 1, 7, 14, 60, and then every 3 months up to 33 months. The percentage of contrast uptake was evaluated on each tumor target by two radiologists and results were compared to PFS. Results: A total of 371 examinations were performed. At d7, the good responders (GR: 25 pts) and poor responders (PR: 11 pts) presented a statistically significant difference in contrast uptake of DCE-US (p=0.004). There was no significant difference between the 2 groups in tumor volume modification (WHO and RECIST criteria at 2 months). After a median follow-up of 510 days, the median PFS of GR an PR were 602 days and 252 days respectively. A resumption of contrast uptake, before any increase in tumor volume was depicted 6 months before any modification of CT-scan in 7 patients. Conclusion: DCE-US is a new functional non invasive imaging technique that allows: 1) to predict after d7 the PFS 2) an early evaluation of secondary resistance to IM. No significant financial relationships to disclose.
춘계학술대회 : 포스터전시 ; 간경변 환자에서 감염발생의 위험요소
Authors: 김상중, 김정욱, 김석원, 김대원, 김형준, 도재혁, 김재규, 장세경, 박실무
Journal: Clinical and Molecular Hepatology (2005)

배경/목적: 간경변 환자의 감염은 흔히 발생하는 치명적인 합병증으로 입원을 요하기도 한다. 하지만 간경변 환자 감염의 위험인자에 대해서는 연구마다 다양한 결과가 보고되고 있다. 이번 연구에서는 입원한 간경변 환자에서 감염증의 위험인자를 알아보았다. 대상 및 방법: 674예의 간경변 환자의 입원을 대상으로 감염의 발생과 질병의 원인, 간기능, 간경변의 진행 및 합병증, 생존율 등과의 연관성을 알아보았다. 감염 양상을 보이는 대상군은 감염군과 원인불명감염군
Assessment of combination treatment with gemcitabine, cisplatin, and methylprednisolone (Gem-P) in the management of non-Hodgkin T-cell lymphoma.
Authors: K. Yim, I. Chau, A. Horwich, C. Dearden, G. Morgan, A. Wotherspoon, A. Attygalle, B. Sharma, D. Cunningham
Journal: Journal of Clinical Oncology (2010)

8052 Background: T-cell lymphoma is rare and generally confers a poorer prognosis compared to B-cell lymphoma but traditionally receive CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone). We investigated the feasibility of a gemcitabine-based regimen. Methods: Between 2000 to 2009, 29 consecutive patients who received Gem-P were identified through our clinical database. Treatment regimen: gemcitabine 1,000 mg/m2 D1, 8, 15 with cisplatin 100 mg/m2 D15 and methylprednisolone 1,000 mg D1-5 of each 28-day cycle. Cisplatin was substituted with oxaliplatin in patients with tinnitus or carboplatin where there was impaired renal function. Two patients also received combination rituximab. Assessment endpoint was response rate. Results: Median age at presentation was 53 years (range 17–72). M:F = 17:12. Stage I 5/29 (17%), stage II 2/29 (7%), stage III 10/29 (35%), stage IV 12/29 (41%). Subtypes included angioimmunoblastic (10), anaplastic large cell (6) [ALK-1 -ve (5), ALK-1 +ve (1)], peripheral T-cell not otherwise specified (6), NK/T-cell (3), adult T-cell leukemia/ lymphoma (2), mycosis fungoides (1), and enteropathy type (1). Patients received between one to six cycles of treatment. Average number of cycles received was 2.2. Overall radiological responses (complete response [CR] and partial response [PR]) were found in 21/29 patients (73%; 95% CI: 53-87%). Objective response rate in first line therapy was 80%. 10/11 of the patients who attained CR had stage III or IV disease. In addition, three patients achieved repeat objective response (1CR, 2PR) when rechallenged at relapse after 6 months or more. Overall grade 3/4 neutropenia and thrombocytopenia rates were 41.4% and 55.2% respectively. Conclusions: Gem-P achieved response both as initial treatment or salvage therapy after multiple line relapse. Prospective randomized trials will be needed to confirm its benefit in this distinct subgroup. Response n= 29 Overall (%) First line Second line Third line Fifth-sixth line CR 11/29 (38) 4/10 (40) 4/9 (45) 2/8 (24) 1/2 (50) PR 10/29 (35) 4/10 (40) 2/9 (22) 3/8 (38) 1/2 (50) Stable 1/29 (3) — 1/9 (11) — — Progressive 7/29 (24) 2/10 (20) 2/9 (22) 3/8 (38) — Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche
PCA-based groupwise image registration for quantitative MRI
Authors: W. Huizinga, D.H.J. Poot, J.-M. Guyader, R. Klaassen, B.F. Coolen, M. van Kranenburg, R.J.M. van Geuns, A. Uitterdijk, M. Polfliet, J. Vandemeulebroucke, A. Leemans, W.J. Niessen, S. Klein
Journal: Medical Image Analysis (2015)
Abstract 320: Decreasing Intraosseous Pressure and Increasing Respiratory Variability Track Fluid Volume Reduction in a Porcine Hypovolemia Model
Authors: Ralph J Frascone, Joshua G Salzman, Peter Bliss, Alex Adams, Sandi S Wewerka, David J Dries
Journal: Circulation (2013)

Objectives: Central venous pressure (CVP) provides an invasive and imprecise but accepted method for estimating fluid volume status. Intraosseous (IO) pressure monitoring may provide an alternative to CVP. To investigate this possibility, we measured intraosseous pressure changes in a porcine model during a hemorrhagic shock protocol. Methods: Our preparation included placement of femoral artery and central venous pressure lines. IO access was obtained by standard technique (EZ-IO, Vidacare Corporation, San Antonio, TX) to monitor pressures in the femur, humerus and tibia. All pressure signals were transmitted to a data acquisition system (Dataq Instruments,Inc., Akron, OH). To create vascular fluid volume changes, 17% of each pig’s estimated total blood volume was bled every 10 minutes until physiologic signs of hemorrhagic shock were recorded (mean arterial pressure &lt;50 mmHg; tachycardia &gt;150/min). To estimate fluid volume status, we tracked changes in absolute arterial, venous and IO pressures. As increasing respiratory variability is an accepted indicator of developing hypovolemia, we evaluated pressure variability due to respiration in all pressures after each 10 minute bleed period using the following formula: Δsystolic pressure/pulse pressure. Results: A hypotensive state was achieved in all six animals after bleeding each animal to 66.1±11.7% (1706.57±210 ml) of their estimated baseline fluid volume. Arterial, CVP and all IO mean pressures decreased at a constant rate. The proportional decrease pre/post bleed (mmHg) was not statistically different among all pressures: arterial 78.5→ 34.0 (-57%), humerus 17.9 → 6.5 (-64%), femur 17.1 → 9.8 (-43%), tibia 14.8 → 8.4 (-43%), CVP 6.6→ -0.9. The respiratory variability ratio increased in arterial, CVP and IO pressures to a similar extent and rate from 0.2 to 0.8 as the hypovolemic state developed. Conclusions: IO pressure decreased consistently at each IO site in this hemorrhagic shock model, indicating IO pressures can be tracked as indicators of change in fluid volume status. Increasing variability in IO pressure during the respiratory cycle was also associated with decreasing vascular fluid volume. IO pressure appears to be equivalent to CVP as an indicator of fluid volume status.
Fas expression in pancreatic adenocarcinoma is related to prognosis
Authors: P. Demetter, S. Claeys, M. Peeters, B. De Hemptinne, C. A. Cuvelier
Journal: Journal of Clinical Oncology (2004)

9695 Background: Based on the histopathological assessment of pancreatic cancer resection specimens, prognostically relevant factors are known. However, the knowledge of additional factors associated with the prognosis might be helpful in planning the therapy for an individual patient. Methods: We investigated paraffin-embedded specimens of 25 patients undergoing surgical treatment for adenocarcinoma by immunohistochemistry to assess the expression and the prognostic impact of p53, Ki-67, Bcl-2, Fas and MMP-9. The number of positive neoplastic cells and the intensity of staining were scored semiquantitatively. The presence of micrometastases in locoregional lymph nodes was studied by staining for low molecular weight-cytokeratins. Neither survival time nor disease-free survival time were known at the time of the investigation. Results: No correlation was established between immunohistochemically detected micrometastases and prognosis.The expression of p53, Ki-67, Bcl-2 and MMP-9 did not influence the survival or disease-free survival. Expression of Fas, however, was associated with longer disease-free survival (P=0.014). Conclusions: Fas exerts an influence on prognosis in adenocarcinoma of the pancreas. However, further investigations in larger patient samples are required to confirm these results. No significant financial relationships to disclose.
Study of pulmonary function in type2 diabetes mellitus and its changes with change in duration and glycemic control
Authors: Salim Zaman, Anilbaran Singhamahapatra, Apurba Mukherjee, Joyashree Banerjee
Journal: European Respiratory Journal (2012)

Rationale : Diabetes mellitus(DM) is a metabolic disease causing changes in multiple systems, and pulmonary system is not an exception to this rule. As the prevalence of T2DM is increasing, the potential implication of diabetic status affecting pulmonary system demand attention.   Objectives : To assess the pulmonary function in Type2 DM patients and its variation(if any) with Duration of disease and level of glycemic control.   Methods : A comparative study was conducted including 60 T2DM patients and 60 age and sex matched controls. The special investigations were done: 1. HBA1c, 2. PFT by flow sensitive spirometer 3.DLCO by single breath technique. Grouping of cases were done according to duration of T2DM (Gr.Ia=≤5yr, Gr.Ib=6-10yr, Gr.Ic=>10yr) and HBA1c level(Gr.IIa= 7).    Results : Significant changes in PFT parameters and Diffusion capacity-DLCO% and DL/VA% in cases compared to controls.There was significant(P   Conclusion : There is significant changes of pulmonary functions with changes in duration and glycemic control, which may be due to non enzymatic glycosylation of tissue proteins and chronic diabetic microangiopathy. So, in routine screening by doing PFT, we can reduce mortality and morbidity of the patients(type2DM) due to subclinical or overt pulmonary dysfunctions.
Verapamil increases the survival of patients with anthracycline-resistant metastatic breast carcinoma
Authors: D Belpomme, S Gauthier, E Pujade-Lauraine, T Facchini, M J Goudier, I Krakowski, G Netter-Pinon, M Frenay, C Gousset, F N Marié, M Benmiloud, F Sturtz
Journal: Annals of Oncology (2000)
Phase II trial of five fractions of radiotherapy followed by four cycles of FOLFOX chemotherapy as preoperative therapy for rectal adenocarcinoma: Report of an interim response analysis.
Authors: R. J. Myerson, S. R. Hunt, B. R. Tan, P. Parikh, A. C. Lockhart, J. Picus, S. Sorscher, R. Suresh, A. Wang-Gillam, J. W. Fleshman, I. J. Kodner
Journal: Journal of Clinical Oncology (2011)

e14003 Background: Preoperative radiotherapy (RT) with 5FU chemotherapy (CT) is a standard of care for cT3-4 rectal cancer. Multi-institution trials incorporating additional cytotoxic agents have resulted in increased morbidity with little benefit. We evaluate a template that seeks to (1) include the known benefits of preoperative RT on local response/control, (2) provide for preoperative multi-drug CT, (3) avoid the morbidity of concurrent RT and multi-drug CT, (4) keep the surgery within 4 weeks of where it would be with conventionally fractionated RT. Methods: Patients with cT3-4, any N, any M rectal cancer were eligible. Patients were confirmed by a surgeon to be candidates for extirpative surgery, provided the response to preoperative treatment was sufficient. Preoperative treatment consisted of 5 fractions of pelvic RT (25 Gy to involved mesorectum, 20 Gy to elective nodes) followed by a 2 week rest, followed by 4 cycles of bi-weekly mFOLFOX6. Surgery was 4-9 weeks after completion of preoperative treatment. Postoperative CT was at the discretion of the treating medical oncologist, but another 6-8 cycles of FOLFOX was recommended. The principal objectives are to demonstrate that this regimen can achieve T stage down staging (ypT < cT) and acute grade 3+ gastrointestinal (GI) morbidity equal to or better than historical controls. Results: Accrual opened November 2009. To date 36 patients have enrolled, with 6 cases experiencing grade 3 acute GI morbidity. Twenty-five cases (all cT3, 18 cN+, 3cM1) have had sufficient time to proceed to surgery. Two were inevaluable: one withdrew consent prior to CT and one received no surgery due to progression of distant disease (with local response). Of the 23 evaluable cases, all had R0 resections, 18 (78%) had ypT0-2 residual disease (6 ypT0 (26%), 4 ypT1, 8 ypT2), 19 (83%) were ypN0. Conclusions: Interim analysis shows that 5 fractions of preoperative RT followed by 4 cycles of FOLFOX is effective in eliciting tumor response. This template preserves the known benefits of radiation therapy on local control while allowing incorporation of full-dose multi-agent chemotherapy.