tbuckley/cabot-search huggingface dataset:
Antibody-mediated leucocyte cytotoxicity to Chang human liver cells in rheumatoid arthritis and other diseases.
Authors: G S Panayi
Journal: Annals of the Rheumatic Diseases (1976)

The incidence of an IgG-antibody which induces lymphocyte cytotoxicity to Chang human liver cells in culture was estimated in the sera of patients with rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, Crohn's disease, ulcerative colitis, and in healthy controls. It was found in 4.1% of control subjects and in 31% of patients with rheumatoid arthritis. None of the other patient groups differed from the control group. This may be the first demonstration of an antibody response to an antigen or antigens which is almost entirely confined to patients with rheumatoid arthritis. The possibility that an antigenic similarity exists between the rheumatoid synovial membrane and Chang cells is currently under investigation.
Imaging of Human Tumor Xenografts With an Indium-111-Labeled Anti-Epidermal Growth Factor Receptor Monoclonal Antibody
Authors: A. Goldenberg, H. Masui, C. Divgi, H. Kamrath, K. Pentlow, J. Mendelsohn
Journal: JNCI Journal of the National Cancer Institute (1989)

The mouse monoclonal antibody (mAb) 225 IgG1 against the epidermal growth factor (EGF) receptor has been investigated for its capacity to localize in human tumor xenografts. The EGF receptor is the product of the c-erb-B proto-oncogene (also known as EGFR). Elevated expression of EGF receptors has been demonstrated in many human tumors and tumor cell lines. We studied A431 human vulvar squamous cell carcinoma cells, with 2 X 10(6) receptors per cell; MDA-MB-468 (MDA 468) human breast adenocarcinoma cells, with 3 X 10(5) receptors per cell; and MCF-7 human breast adenocarcinoma cells, with 5 X 10(3) receptors per cell. The 111In-labeled pentetic acid (DTPA), derivative of mAb 225 (111In-DTPA-225) was injected intraperitoneally into nude mice bearing subcutaneous tumor xenografts. We measured uptake by quantifying radioactivity in tumor and normal tissues and by obtaining gamma camera images. Uptake in A431 xenografts was 28% +/- 2.4% of the injected dose per gram of tumor on day 3 and 12.4% +/- 3.0% on day 7. Distribution ratios comparing uptake in the tumor with that in normal tissues were consistently greater than 4. In contrast, there was far less uptake of the control mAb KS1/4S-1 labeled with 111In. This conjugate, 111In-DTPA-KS1/4S-1, has an IgG1 isotype but does not bind to human or murine cells. Imaging of the tumor with mAb 225 was excellent, especially on days 3-7. MDA 468 xenografts exhibited reduced localization of mAb 225 in the tumor. For MCF-7 xenografts, the tumor uptake of mAb 225 after 7 days was only 0.70% +/- 0.10% of the injected dose per gram of tumor, which was comparable to the uptake of the KS1/4S-1 control mAb. The ratio of the concentration of radioactivity in the tumor to that in normal tissue (distribution ratio) showed poor selectivity of uptake, and imaging was not obtained. These observations suggest that labeled mAb can target the product of a proto-oncogene, the EGF receptor, when it is expressed at high levels in human tumor xenografts.
Diastolic dysfunction is associated with poor survival in patients with cirrhosis with transjugular intrahepatic portosystemic shunt
Authors: M. Cazzaniga, F. Salerno, G. Pagnozzi, E. Dionigi, S. Visentin, I. Cirello, D. Meregaglia, A. Nicolini
Journal: Gut (2006)

<b>Background:</b> Transjugular intrahepatic portosystemic shunt (TIPS) is a treatment for portal hypertension-related complications. Accurate prediction of the outcome of patients treated with TIPS is important, because some patients have very short survival. Diastolic dysfunction is frequently observed in patients with cirrhosis. <b>Aim:</b> To investigate whether or not diastolic dysfunction can predict the outcome after TIPS. <b>Methods:</b> Echocardiography with Doppler exploration was performed before and 28 days after TIPS insertion in 32 patients with cirrhosis. Several echocardiographic measures, including the early maximal ventricular filling velocity/late filling velocity (E/A) ratio as indicative of diastolic function, as well as laboratory, clinical and demographic variables were evaluated as predictors of survival. <b>Results:</b> Univariate analysis revealed that the presence of diastolic dysfunction observed 28 days after TIPS (E/A ratio ⩽1) and baseline model of end-stage liver disease score were related to survival. Multivariate analysis identified diastolic dysfunction as an independent predictor of death (RR 8.9, 95% CI 1.9 to 41.5, p = 0.005). During the first year of follow–up, six out of 10 patients with an E/A ratio ⩽1 died, whereas all 22 patients with E/A ratio &gt;1 survived. <b>Conclusions:</b> Diastolic dysfunction estimated using E/A ratio is a promising predictor of death in patients with cirrhosis who are treated with TIPS.
Effect of methylprednisolone upon technetium-99m pyrophosphate assessment myocardial necrosis in the canine countershock model.
Authors: R M Schneider, J P Hayslett, S E Downing, H J Berger, R K Donabedian, B L Zaret
Journal: Circulation (1977)

Repeat DC countershock reproducibly results in myocardial necrosis in dogs. In this model, myocardial technetium-99m pyrophosphate (PYP) uptake correlates linearly with tissue creatine kinase depletion (r = -0.83). The effect of pretreatment with methylprednisolone (MP) was studied with PYP in 25 dogs. In myocardium damaged by countershock, 12 MP dogs had higher tissue radioactivity sample:normal (S:N) ratios than control (P less than 0.05), suggesting increased tissue injury. However, by several other measures of tissue damage, the two groups did not differ. MP-elevated PYP S:N ratios were explained by reduced PYP activity in normal myocardium of MP dogs. Further experiments in 21 dogs revealed that renal PYP clearance, which correlated with glomerular filtration rate (GFR) as measured by creatinine clearance, was increased in Mp dogs, resulting in accelerated urinary excretion of PYP (46.9+/-3.6 vs 35.8+/-2.4 percent injected dose in one hour, P less than 0.01), and reduced blood PYP. Thus MP does not modify countershock-induced myocardial injury. However, by increasing GFR, MP increased PYP excretion, resulting in lowered blood and normal zone myocardial PYP, thereby spuriously affecting myocardial PYP tissue uptake data.
CALR and ASXL1 mutations-based molecular prognostication in primary myelofibrosis: an international study of 570 patients
Authors: A Tefferi, P Guglielmelli, T L Lasho, G Rotunno, C Finke, C Mannarelli, A A Belachew, A Pancrazzi, E A Wassie, R P Ketterling, C A Hanson, A Pardanani, A M Vannucchi
Journal: Leukemia (2014)

Current prognostication in primary myelofibrosis (PMF) is based on the dynamic international prognostic scoring system (DIPSS)-plus, which employs clinical and cytogenetic variables. We recently reported DIPSS-plus independent prognostic significance for calreticulin (CALR) (favorable) and ASXL1 (unfavorable) mutations. In the current study, 570 PMF patients were recruited for derivation (n=277) and validation (n=293) of a molecular prognostic model based on these two mutations. Survival was the longest in CALR(+)ASXL1(-) (median 10.4 years) and shortest in CALR(-)ASXL1(+) patients (median, 2.3 years; hazard ratio (HR), 5.9; 95% confidence interval (CI), 3.5-10.0). CALR(+)ASXL1(+) and CALR(-)ASXL1(-) patients had similar survival and were grouped together in an intermediate-risk category (median survival, 5.8 years; HR, 2.5; 95% CI, 1.5-4.0). The CALR/ASXL1 mutations-based prognostic model was DIPSS-plus independent (P<0.0001) and effective in identifying low-/intermediate-1-risk patients with shorter (median, 4 years) or longer (median 20 years) survival and high-/intermediate-2-risk patients with shorter (median, 2.3 years) survival. Multivariable analysis distinguished CALR(-)ASXL1(+) mutational status as the most significant risk factor for survival: HR 3.7 vs 2.8 for age >65 years vs 2.7 for unfavorable karyotype. These observations signify immediate clinical relevance and warrant i) CALR and ASXL1 mutation determination in all patients with PMF and ii) molecular revision of DIPSS-plus.
The Effect of Emergency Department Copayments for Medicaid Beneficiaries Following the Deficit Reduction Act of 2005
Authors: Mona Siddiqui, Eric T. Roberts, Craig E. Pollack
Journal: JAMA Internal Medicine (2015)

High unemployment during the 2007-2009 Great Recession and eligibility expansions have increased the size and cost of Medicaid. To provide states with flexibility in administering the program while containing costs, the Deficit Reduction Act of 2005 (DRA) gave states the authority to impose cost-sharing strategies, including emergency department (ED) copayments for nonurgent visits. To our knowledge, there has been no previous longitudinal analysis of the effect of the DRA on health care utilization outcomes for Medicaid beneficiaries.
Emphysema: time to say farewell to therapeutic nihilism
Authors: Zaid Zoumot, Simon Jordan, Nicholas S Hopkinson
Journal: Thorax (2014)

It is an interesting time for the management of emphysema. In this condition, destruction of lung parenchyma associated with reduced elastic recoil and dynamic airways closure produce gas trapping and increased operating lung volumes, leading to breathlessness and exercise limitation. It has historically been defined as an irreversible process, which has led to a degree of therapeutic nihilism. One manifestation of this has been the curious neglect of lung volume reduction surgery (LVRS). Clinical guidelines,1 reflecting trial evidence,2 recommend consideration of LVRS in selected patients with upper lobe predominant emphysema and poor exercise capacity, the phenotype where surgery has been shown to produce a survival benefit. Modern surgical techniques, unilateral treatment and improved postoperative care and patient selection mean that LVRS is also associated with lower morbidity and mortality than data published at the turn of the century had suggested,3 ,4 with one recent case series reporting zero 90-day mortality following unilateral surgery.5

Nevertheless, little effort seems to be going into identifying this patient population and LVRS remains vastly underused with just 90 procedures taking place in the UK in 2010–2011. A partial explanation for this may be found in a recent survey of British Thoracic Society members that revealed that a significant proportion overestimated the morbidity and mortality associated with LVRS.6 Only 30% had access to a dedicated chronic obstructive pulmonary disease (COPD) multidisciplinary meeting to review patients, and there was no consensus as to the correct strategy to adopt to identify appropriate patients.

Over the last decade, bronchoscopic approaches for lung volume reduction in emphysema have proliferated. These include one-way endobronchial valves to induce lobar collapse,7–10 airway bypass approaches to create low-resistance extra-anatomical pathways that allow trapped …
Effect of 2-Week Treatment With Pirenzepine on Fasting and Postprandial Glucose Concentrations in Individuals With Type 2 Diabetes
Authors: Basil G. Issa, Nichola Davies, Kerenza Hood, Lakdasa D.K.E. Premawardhana, John R. Peters, Maurice F. Scanlon
Journal: Diabetes Care (2003)

Results from a population-based survey Our objective was to evaluate the diagnostic proficiency of the World Health Organization (WHO) and the National Cholesterol Education Program (NCEP)-III definitions (1,2) for the metabolic syndrome in a Mexican nationwide, population-based survey.Details of the sampling procedures have been previously described (3).The population was composed of 2,158 men and women aged 20 -69 years sampled after a 9-to 12-h fasting period.For the WHO criteria, insulin resistance was diagnosed if a nondiabetic case had fasting insulin concentrations Ն126 pmol/l (21 U/ml) (Ͼ75th percentile in Mexican adults).The ageadjusted prevalence was 13.61% for the WHO criteria (n ϭ 268) and 26.6% for the NCEP-III definition (n ϭ 574).After excluding patients with diabetes, the prevalence was 9.2 and 21.4%, respectively.The agreement between the definitions was assessed in 1,969 subjects; 189 cases were eliminated due to the lack of a urine sample.The number of abnormal cases was lower using the WHO criteria.Only 237 of the 545 subjects (43.4%) who fulfilled the NCEP criteria were diagnosed as affected using the WHO definition.Just 16 of 253 cases (6.3%) detected by the WHO definition did not fulfill the NCEP definition.The agreement between the criteria was moderate ( ϭ 0.507).On the other hand, the subjects diagnosed using the WHO recommendations had a worse profile than the cases detected by the NCEP-III definition only-they had a higher BMI and higher non-HDL cholesterol, triglyceride, and glucose concentrations.The demonstration of insulin resistance among the nondiabetic population caused the lack of agreement in 202 of the 242 cases that fulfilled the NCEP definition but failed the WHO criteria.Other reasons for disparity were the higher thresholds used by the WHO criteria; these differences explained the lack of agreement in 66 of the 152 cases with diabetes.In conclusion, the prevalence of the metabolic syndrome is influenced by the selection of the diagnostic criteria.The WHO criteria identified a lower number of cases than the NCEP-III definition.These differences were explained mainly by the inclusion of abnormally high insulin concentrations as a diagnostic criterion.However, the presence of insulin resistance may help to identify patients more severely affected (4).
Phase I Clinical and Pharmacokinetic Study of the Novel Raf Kinase and Vascular Endothelial Growth Factor Receptor Inhibitor BAY 43-9006 in Patients With Advanced Refractory Solid Tumors
Authors: Dirk Strumberg, Heike Richly, Ralf A. Hilger, Norbert Schleucher, Sonke Korfee, Mitra Tewes, Markus Faghih, Erich Brendel, Dimitris Voliotis, Claus G. Haase, Brian Schwartz, Ahmad Awada, Rudolf Voigtmann, Max E. Scheulen, Siegfried Seeber
Journal: Journal of Clinical Oncology (2004)

BAY 43-9006 is a novel dual-action Raf kinase and vascular endothelial growth factor receptor inhibitor that inhibits tumor cell proliferation and angiogenesis. This study established the safety and pharmacokinetics of BAY 43-9006 in 69 patients with advanced refractory solid tumors.BAY 43-9006 (50 to 800 mg) was administered once or twice daily on a varying weekly schedule. Pharmacokinetic sampling was performed in all patients; preliminary tumor response was also assessed. The effect of BAY 43-9006 on phorbol myristate acetate-stimulated ERK phosphorylation in peripheral blood lymphocytes was studied using flow cytometry.Mild to moderate diarrhea was the most common (55%) treatment-related adverse event. The maximum-tolerated dose was 400 mg bid continuous. Dose-limiting toxicities were grade 3 diarrhea and fatigue at 800 mg bid, and grade 3 skin toxicity at 600 mg bid. BAY 43-9006 pharmacokinetics were highly variable for single and multiple dosing, and toxicity did not appear to be dose dependent. Significant decreases of phorbol myristate acetate-stimulated ERK phosphorylation (P < .01) were identified at doses >/= 200 mg bid continuous. Forty-five patients were assessable for efficacy; one patient had a partial response (hepatocellular carcinoma at 400 mg bid continuous), 25 patients had stable disease, with eight lasting > 6 months and five for >12 months. Eighteen patients had progressive disease, and tumor response could not be evaluated in one patient.Oral BAY 43-9006 was well tolerated and appeared to provide some clinical benefits. Based on the results of this study, BAY 43-9006 at 400 mg bid continuous is recommended for ongoing and future studies.
WASP regulates suppressor activity of human and murine CD4+CD25+FOXP3+ natural regulatory T cells
Authors: Francesco Marangoni, Sara Trifari, Samantha Scaramuzza, Cristina Panaroni, Silvana Martino, Luigi D. Notarangelo, Zeina Baz, Ayse Metin, Federica Cattaneo, Anna Villa, Alessandro Aiuti, Manuela Battaglia, Maria-Grazia Roncarolo, Loïc Dupré
Journal: The Journal of Experimental Medicine (2007)

A large proportion of Wiskott-Aldrich syndrome (WAS) patients develop autoimmunity and allergy. CD4+CD25+FOXP3+ natural regulatory T (nTreg) cells play a key role in peripheral tolerance to prevent immune responses to self-antigens and allergens. Therefore, we investigated the effect of WAS protein (WASP) deficiency on the distribution and suppressor function of nTreg cells. In WAS−/− mice, the steady-state distribution and phenotype of nTreg cells in the thymus and spleen were normal. However, WAS−/− nTreg cells engrafted poorly in immunized mice, indicating perturbed homeostasis. Moreover, WAS−/− nTreg cells failed to proliferate and to produce transforming growth factor β upon T cell receptor (TCR)/CD28 triggering. WASP-dependent F-actin polarization to the site of TCR triggering might not be involved in WAS−/− nTreg cell defects because this process was also inefficient in wild-type (WT) nTreg cells. Compared with WT nTreg cells, WAS−/− nTreg cells showed reduced in vitro suppressor activity on both WT and WAS−/− effector T cells. Similarly, peripheral nTreg cells were present at normal levels in WAS patients but failed to suppress proliferation of autologous and allogeneic CD4+ effector T cells in vitro. Thus, WASP appears to play an important role in the activation and suppressor function of nTreg cells, and a dysfunction or incorrect localization of nTreg cells may contribute to the development of autoimmunity in WAS patients.
Patient-Centric Blood Pressure–targeted Cardiopulmonary Resuscitation Improves Survival from Cardiac Arrest
Authors: Robert M. Sutton, Stuart H. Friess, Maryam Y. Naim, Joshua W. Lampe, George Bratinov, Theodore R. Weiland, Mia Garuccio, Vinay M. Nadkarni, Lance B. Becker, Robert A. Berg
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Although current resuscitation guidelines are rescuer focused, the opportunity exists to develop patient-centered resuscitation strategies that optimize the hemodynamic response of the individual in the hopes to improve survival.To determine if titrating cardiopulmonary resuscitation (CPR) to blood pressure would improve 24-hour survival compared with traditional CPR in a porcine model of asphyxia-associated ventricular fibrillation (VF).After 7 minutes of asphyxia, followed by VF, 20 female 3-month-old swine randomly received either blood pressure-targeted care consisting of titration of compression depth to a systolic blood pressure of 100 mm Hg and vasopressors to a coronary perfusion pressure greater than 20 mm Hg (BP care); or optimal American Heart Association Guideline care consisting of depth of 51 mm with standard advanced cardiac life support epinephrine dosing (Guideline care). All animals received manual CPR for 10 minutes before first shock. Primary outcome was 24-hour survival.The 24-hour survival was higher in the BP care group (8 of 10) compared with Guideline care (0 of 10); P = 0.001. Coronary perfusion pressure was higher in the BP care group (point estimate +8.5 mm Hg; 95% confidence interval, 3.9-13.0 mm Hg; P < 0.01); however, depth was higher in Guideline care (point estimate +9.3 mm; 95% confidence interval, 6.0-12.5 mm; P < 0.01). Number of vasopressor doses before first shock was higher in the BP care group versus Guideline care (median, 3 [range, 0-3] vs. 2 [range, 2-2]; P = 0.003).Blood pressure-targeted CPR improves 24-hour survival compared with optimal American Heart Association care in a porcine model of asphyxia-associated VF cardiac arrest.
Effect of age on the thickness of adult articular cartilage at he shoulder joint.
Authors: G Meachim
Journal: Annals of the Rheumatic Diseases (1971)

Human articular cartilage can develop areas of fibrillation.In such areas there is fraying and splitting of the cartilage, frequently accompanied by its local disintegration and erosion.Collins (1949) regarded all grades of fibrillation as forms of 'osteo- arthritic' cartilage change, although he recognized that many of the destructive lesions found at nec- ropsy are mild and appear to have been clinically asymptomatic.In man, areas of cartilage fibrillation become
Selective Estrogen Receptor Modulator Idoxifene Inhibits Smooth Muscle Cell Proliferation, Enhances Reendothelialization, and Inhibits Neointimal Formation In Vivo After Vascular Injury
Authors: T.-L. Yue, L. Vickery-Clark, C. S. Louden, J.-L. Gu, X. L. Ma, P. K. Narayanan, X. Li, J. Chen, B. Storer, R. Willette, K. A. Gossett, E. H. Ohlstein
Journal: Circulation (2000)

Idoxifene (ID) is a tissue-selective estrogen receptor modulator (SERM). The pharmacological profile of ID in animal studies suggests that it behaves like an estrogen receptor (ER) agonist in bone and lipid metabolism while having negligible ER activity on the reproductive system. It is unknown whether ID retains the vascular protective effects of estrogen.In cultured vascular smooth muscle cells (VSMCs), ID inhibited platelet-derived growth factor-induced DNA synthesis and mitogenesis with IC(50) values of 20.4 and 27.5 nmol/L, respectively. Treatment with ID resulted in S-phase cell cycle arrest in serum-stimulated VSMCs. ID 1 to 100 nmol/L significantly protected endothelial cells from tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis in vitro. Virgin Sprague-Dawley rats ovariectomized 1 week before the study were treated with ID (1 mg x kg(-1) x d(-1)) or vehicle by gavage for 3 days before balloon denudation in carotid artery. The SMC proliferation in injured vessels was determined by immunostaining for proliferating cell nuclear antigen (PCNA). The number of PCNA-positive SMCs was reduced by 69%, 82%, and 86% in the media at days 1, 3 and 7, respectively, and by 78% in the neointima at day 7 after injury in ID- versus vehicle-treated group (P:<0.01). ID significantly enhanced reendothelialization in the injured carotid arteries as determined by Evans blue stain and immunohistochemical analysis for von Willebrand factor. In the former assay, the reendothelialized area in injured vessels was 43% in ID-treated group versus 24% in the vehicle group (P:<0.05); in the latter assay, the numbers of von Willebrand factor-positive cells per cross section increased from 24. 8 (vehicle) to 60.5 (ID) (P:<0.01) at day 14 after injury. In addition, the production of nitric oxide from excised carotid arteries was significantly higher in ID-treated than the vehicle group (8.5 versus 2.7 nmol/g, P:<0.01). Finally, ID treatment reduced neointimal area and the ratio of intima to media by 45% and 40%, respectively (P:<0.01), at day 14 after balloon angioplasty.The results indicate that ID beneficially modulates the balloon denudation-induced vascular injury response. Inhibition of VSMC proliferation and acceleration of endothelial recovery likely mediate this protective effect of ID.