tbuckley/cabot-search huggingface dataset:
Autoreactive T cells bypass negative selection and respond to self-antigen stimulation during infection
Authors: Sarah Enouz, Lucie Carrié, Doron Merkler, Michael J. Bevan, Dietmar Zehn
Journal: The Journal of Experimental Medicine (2012)

Central and peripheral tolerance prevent autoimmunity by deleting the most aggressive CD8+ T cells but they spare cells that react weakly to tissue-restricted antigen (TRA). To reveal the functional characteristics of these spared cells, we generated a transgenic mouse expressing the TCR of a TRA-specific T cell that had escaped negative selection. Interestingly, the isolated TCR matches the affinity/avidity threshold for negatively selecting T cells, and when developing transgenic cells are exposed to their TRA in the thymus, only a fraction of them are eliminated but significant numbers enter the periphery. In contrast to high avidity cells, low avidity T cells persist in the antigen-positive periphery with no signs of anergy, unresponsiveness, or prior activation. Upon activation during an infection they cause autoimmunity and form memory cells. Unexpectedly, peptide ligands that are weaker in stimulating the transgenic T cells than the thymic threshold ligand also induce profound activation in the periphery. Thus, the peripheral T cell activation threshold during an infection is below that of negative selection for TRA. These results demonstrate the existence of a level of self-reactivity to TRA to which the thymus confers no protection and illustrate that organ damage can occur without genetic predisposition to autoimmunity.
Contingency Management for Treatment of Substance Abuse
Authors: Maxine Stitzer, Nancy Petry
Journal: Annual Review of Clinical Psychology (2006)

Clinical research trials demonstrate the efficacy of contingency management procedures in treating substance use disorders. Usually, reinforcement, in the form of vouchers exchangeable for retail goods and services, is provided for drug abstinence in patients treated in psychosocial or methadone maintenance clinics. Recently, the types of reinforcers have been adapted to include lower cost alternatives, and reinforcement is being expanded to alter other target behaviors such as attendance at treatment, adherence to treatment goals, and compliance with medication. This chapter provides an overview of the populations and behaviors to which contingency management approaches have been applied. It also reviews design features that appear critical in the successful adaptation of the techniques. In addition, areas for future research are described.
Antipyrine clearance and response to interferon treatment in patients with chronic active hepatitis C
Authors: Shirley Coverdale, Karen Byth, Jacqueline Field, Christopher Liddle, Rita Lin, Geoffrey C. Farrell
Journal: Hepatology (1995)

To determine whether hepatic metabolic function affects the response to interferon treatment, we measured antipyrine clearance (APC) in 85 patients with chronic active hepatitis C and compared the results with treatment outcome. Among 55 patients who responded to interferon by normalization of alanine transaminase (ALT), median APC before treatment was 0.47 (range, 0.12 to 0.98; normal range, 0.34 to 1.02 mL/min/kg body wt), a value that was significantly greater than in 30 nonresponders (0.23; 0.08 to 0.67 mL/min/kg body wt, P &lt; .001). APC was closely associated with response to interferon. The response rate among cases with values &gt;0.25 mL/min/kg body weight was 79%, the same as in cases without cirrhosis. Cases without cirrhosis and with APC of &gt;0.25 mL/min/kg body weight had an 85% chance of responding to interferon; this was unlikely a simple reflection of histological activity, because the correlation with Scheuer score was poor in this subgroup ( r = -.31, P &lt; .05). A second, independent group of 43 patients was used to test the predictive value of APC (using 0.25 mL/min/kg body wt as a cut-off) for response to interferon treatment. In this group, APC correctly predicted positive response to interferon in 75% of cases. APC was also used to measure the effects of treatment on hepatic metabolic function. Regardless of outcome, there was no change in APC at the end of a 6-month course of interferon treatment. Six months later, however, improvement in APC (14%; P &lt; .05) was evident among responders but not in those who had failed to respond to interferon. In patients who continued to have normal ALT (18 of 19 tested were also nonviremic), the improvement in APC was sustained for at least 24 months, whereas among relapsers (defined by ALT increase), APC eventually declined to be less than the pretreatment value at 24 months. It is concluded that pretreatment APC is a powerful positive predictor of responsiveness to interferon treatment in patients with chronic hepatitis C, indicating that good hepatic metabolic function may be important in determining the effectiveness of interferon treatment. Furthermore, changes in hepatic metabolic function after apparently successful treatment, at least as determined by APC, appear to be subtle, delayed in onset, and maintained only in those who remain in biochemical remission. (Hepatology 1995; 22:1065-1071.).
Response to Letter Regarding Article, “Mechanisms of Preejection and Postejection Velocity Spikes in Left Ventricular Myocardium: Interaction Between Wall Deformation and Valve Events”
Authors: Espen W. Remme, Erik Lyseggen, Thomas Helle-Valle, Eirik Pettersen, Asgrimur Ragnarsson, Halfdan Ihlen, Thor Edvardsen, Otto A. Smiseth, Anders Opdahl, Trond Vartdal, Morten Ljosland
Journal: Circulation (2009)
Perceptions of Patients and Physicians Regarding Phase I Cancer Clinical Trials: Implications for Physician-Patient Communication
Authors: Neal J. Meropol, Kevin P. Weinfurt, Caroline B. Burnett, Andrew Balshem, Al B. Benson, Liana Castel, Sandra Corbett, Michael Diefenbach, Darrell Gaskin, Yun Li, Sharon Manne, John Marshall, Julia H. Rowland, Elyse Slater, Daniel P. Sulmasy, David Van Echo, Shakira Washington, Kevin A. Schulman
Journal: Journal of Clinical Oncology (2003)

To describe and compare the perceptions of cancer patients and their physicians regarding phase I clinical trials.Eligible patients had been offered phase I trial participation and had decided to participate but had not yet begun treatment. Each patient's physician also served as a study subject. Patients and physicians completed questionnaires with domains including perceptions of potential benefit and harm from treatment (experimental and standard), relative value of quality and length of life, and perceived content of patient-physician consultations.Three hundred twenty-eight patients and 48 physicians completed surveys. Patients had high expectations regarding treatment outcomes (eg, median 60% benefit from experimental therapy), with those choosing to participate in a phase I trial being more optimistic than those declining phase I participation. Patients predicted a higher likelihood of both benefit and adverse reactions from treatment (experimental and standard) than their physicians (P <.0001 for all comparisons). Although 95% of patients reported that quality of life was at least as important as length of life, only 28% reported that changes in quality of life with treatment were discussed with their physicians. In contrast, 73% of physicians reported that this topic was discussed (P <.0001).Cancer patients offered phase I trial participation have expectations for treatment benefit that exceed those of their physicians. The discordant perceptions of patients and physicians may possibly be explained by patient optimism and confidence; however, the discrepancies in reports of consultation content, particularly given patients' stated values regarding quality of life, raise the possibility that communication in this context is suboptimal.
Thalassaemic trait and systemic lupus erythematosus
Authors: G Castellino
Journal: Annals of the Rheumatic Diseases (2005)

In conclusion, infliximab can be used safely in daily clinical practice, but both doctors and patients should be aware of the (infection) risks, especially in patients receiving a higher dose (.3 mg/kg) of infliximab, in order to anticipate and minimise these risks.
Are all high-grade breast cancers with no steroid receptor hormone expression alike? The special case of the medullary phenotype
Authors: L. Orlando, G. Renne, A. Rocca, G. Curigliano, M. Colleoni, G. Severi, G. Peruzzotti, G. Viale, G. Sanna, A. Goldhirsch, S. Cinieri
Journal: Annals of Oncology (2005)
Comparison of magnetic resonance imaging colonography with conventional colonoscopy for the assessment of intestinal inflammation in patients with inflammatory bowel disease: a feasibility study
Authors: A. G. Schreyer, H. C. Rath, R. Kikinis, M. Völk, J. Schölmerich, S. Feuerbach, G. Rogler, J. Seitz, Hans H Herfarth
Journal: Gut (2005)

<b>Aim:</b> Magnetic resonance imaging (MRI) based colonography represents a new imaging tool which has mainly been investigated for polyp screening. To evaluate this approach for patients with inflammatory bowel disease (IBD), we compared MRI based colonography with conventional colonoscopy for assessing the presence and extent of colonic inflammation. <b>Patients and methods:</b> In 22 consecutive patients with suspected or known IBD, MRI colonography was performed immediately before conventional colonoscopy. After bowel cleansing, a T1 positive contrast agent was applied rectally. In addition to T2 weighted sequences, T1 weighted two dimensional and three dimensional Flash acquisitions as well as volume rendered virtual endoscopy were performed. All images were evaluated with regard to typical MRI features of inflammation. The results were compared with colonoscopy findings. <b>Results:</b> Distension and image quality was assessed as good to fair in 97.4% of all colonic segments. Only four of 154 segments were considered non-diagnostic. With colonoscopy serving as the gold standard, the sensitivity for correctly identifying inflammation on a per segment analysis of the colon was 31.6% for Crohn’s disease (CD) and 58.8% for ulcerative colitis (UC). In CD, in most cases mild inflammation was not diagnosed by MRI while in UC even severe inflammation was not always depicted by MRI. Virtual endoscopy did not add any relevant information. <b>Conclusion:</b> MRI based colonography is not suitable for adequately assessing the extent of colonic inflammation in patients with IBD. Only severe colonic inflammation in patients with CD can be sufficiently visualised.
Carbonated Soft Drinks and Risk of Esophageal Adenocarcinoma: A Population-Based Case–Control Study
Authors: Jesper Lagergren, Pernilla Viklund, Catarina Jansson
Journal: JNCI Journal of the National Cancer Institute (2006)

The increased intake of carbonated soft drinks parallels the incidence of esophageal adenocarcinoma. To determine whether an association exists between carbonated drink intake and esophageal and cardia adenocarcinoma, we analyzed data from a Swedish nationwide, population-based, case-control study. During data collection in 1995-1997, 189 patients with esophageal adenocarcinoma (88% of all eligible), 262 patients with cardia adenocarcinoma (84%), and 820 control subjects (73%) were interviewed in person. All cancers were histologically classified. We calculated odds ratios with 95% confidence intervals using conditional logistic regression and multivariable analyses. Frequency of intake of carbonated soft drinks was not associated with risk of esophageal adenocarcinoma; high consumers (intake more than six times weekly) were at a statistically nonsignificantly decreased risk compared with never users (odds ratio = 0.89, 95% confidence interval = 0.49 to 1.64). Consumption of carbonated low-alcohol beer and combined intake of carbonated drinks were not associated with risk of esophageal adenocarcinoma. No association between intake of carbonated soft drinks or low-alcohol beer and risk of cardia adenocarcinoma was observed.
Staphylococcal complement evasion by various convertase-blocking molecules
Authors: Ilse Jongerius, Jörg Köhl, Manoj K. Pandey, Maartje Ruyken, Kok P.M. van Kessel, Jos A.G. van Strijp, Suzan H.M. Rooijakkers
Journal: The Journal of Experimental Medicine (2007)

To combat the human immune response, bacteria should be able to divert the effectiveness of the complement system. We identify four potent complement inhibitors in Staphylococcus aureus that are part of a new immune evasion cluster. Two are homologues of the C3 convertase modulator staphylococcal complement inhibitor (SCIN) and function in a similar way as SCIN. Extracellular fibrinogen-binding protein (Efb) and its homologue extracellular complement-binding protein (Ecb) are identified as potent complement evasion molecules, and their inhibitory mechanism was pinpointed to blocking C3b-containing convertases: the alternative pathway C3 convertase C3bBb and the C5 convertases C4b2aC3b and C3b2Bb. The potency of Efb and Ecb to block C5 convertase activity was demonstrated by their ability to block C5a generation and C5a-mediated neutrophil activation in vitro. Further, Ecb blocks C5a-dependent neutrophil recruitment into the peritoneal cavity in a mouse model of immune complex peritonitis. The strong antiinflammatory properties of these novel S. aureus–derived convertase inhibitors make these compounds interesting drug candidates for complement-mediated diseases.
Homoeopathy for delayed onset muscle soreness: a randomised double blind placebo controlled trial.
Authors: A J Vickers, P Fisher, C Smith, S E Wyllie, G T Lewith
Journal: British Journal of Sports Medicine (1997)

OBJECTIVE: To pilot a model for determining whether a homoeopathic medicine is superior to placebo for delayed onset muscle soreness (DOMS). DESIGN: Randomised double blind placebo controlled trial. SETTING: Physiotherapy department of a homoeopathic hospital. SUBJECTS: Sixty eight healthy volunteers (average age 30; 41% men) undertook a 10 minute period of bench stepping carrying a small weight and were randomised to a homoeopathic medicine or placebo. OUTCOME MEASURES: Mean muscle soreness in the five day period after the exercise test, symptom free days, maximum soreness score, days to no soreness, days on medication. RESULTS: The difference between group means was 0.17 in favour of placebo with 95% confidence intervals +/- 0.50. Similar results were found for other outcome measures. CONCLUSION: The study did not find benefit of the homoeopathic remedy in DOMS. Bench stepping may not be an appropriate model to evaluate the effects of a treatment on DOMS because of wide variation between subject soreness scores.
Src Kinase and Mitogen-Activated Protein Kinases in the Progression from Normal to Malignant Endometrium
Authors: Mohamed Mokhtar Desouki, Brian G. Rowan
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of this research was to determine whether a correlation exists between the levels of activated mitogen-activated protein kinase (MAPK) and Src kinases and the progression from normal to malignant endometrium. Experimental Design: We measured total and phosphorylated levels for extracellular signal-regulated kinase 1/2, p38, stress-activated protein kinase/c-Jun NH2-terminal kinase, and Src kinases from 33 frozen endometrial adenocarcinomas and 38 benign endometrial specimens by quantitation of signals from Western blots using antibodies against these kinases. Results: Elevated phospho-extracellular signal-regulated kinase 1/2 (150 ± 40 versus 46 ± 7; P = 0.03), phospho-Src (28 ± 5 versus 4 ± 1), and phospho-p38 (131 ± 16 versus 27 ± 7; P &amp;lt; 0.001) was detected in benign versus malignant endometrium when the Western blot signal of activated kinase was normalized to total kinase levels and β actin. A modest increase in active c-Jun NH2-terminal kinase was detected in carcinoma versus benign specimens (51 ± 13 versus 43 ± 10; P = 0.8). Expression of total kinases (normalized to β-actin) was higher in carcinoma versus benign specimens, respectively (extracellular signal-regulated kinase 1/2, 9 ± 2 versus 0.7 ± 0.1; Src, 7 ± 2 versus 0.4 ± 0.1; stress-activated protein kinase c-Jun NH2-terminal kinase, 2 ± 0.4 versus 0.2 ± 0.02; P &amp;lt; 0.001; and p38, 1 ± 0.2 versus 0.4 ± 0.1; P &amp;lt; 0.01). Immunohistochemistry for active and total Src kinases and MAPKs detected positive staining in epithelial and stroma cells. Conclusions: These data demonstrated that, in contrast with breast cancer, the progression from normal to malignant endometrium is not associated with activation of MAPK and Src kinases. Elevation of these active kinases in benign endometrium may contribute to endometrial resistance to the antiestrogen action of tamoxifen.
Thalidomide for treatment of multiple myeloma: 10 years later
Authors: Antonio Palumbo, Thierry Facon, Pieter Sonneveld, Joan Bladè, Massimo Offidani, Francesca Gay, Philippe Moreau, Anders Waage, Andrew Spencer, Heinz Ludwig, Mario Boccadoro, Jean-Luc Harousseau
Journal: Blood (2008)
Ang-2-VEGF-A CrossMab, a Novel Bispecific Human IgG1 Antibody Blocking VEGF-A and Ang-2 Functions Simultaneously, Mediates Potent Antitumor, Antiangiogenic, and Antimetastatic Efficacy
Authors: Yvonne Kienast, Christian Klein, Werner Scheuer, Romi Raemsch, Erica Lorenzon, Dirk Bernicke, Frank Herting, Sidney Yu, Huynh Hung The, Laurent Martarello, Christian Gassner, Kay-Gunnar Stubenrauch, Kate Munro, Hellmut G. Augustin, Markus Thomas
Journal: Clinical Cancer Research (2013)

VEGF-A blockade has been clinically validated as a treatment for human cancers. Angiopoietin-2 (Ang-2) expression has been shown to function as a key regulator of tumor angiogenesis and metastasis.We have applied the recently developed CrossMab technology for the generation of a bispecific antibody recognizing VEGF-A with one arm based on bevacizumab (Avastin), and the other arm recognizing Ang-2 based on LC06, an Ang-2 selective human IgG1 antibody. The potency of Ang-2-VEGF CrossMab was evaluated alone and in combination with chemotherapy using orthotopic and subcutaneous xenotransplantations, along with metastasis analysis by quantitative real-time Alu-PCR and ex vivo evaluation of vessels, hypoxia, proliferation, and apoptosis. The mechanism of action was further elucidated using Western blotting and ELISA assays.Ang-2-VEGF-A CrossMab showed potent tumor growth inhibition in a panel of orthotopic and subcutaneous syngeneic mouse tumors and patient or cell line-derived human tumor xenografts, especially at later stages of tumor development. Ang-2-VEGF-A CrossMab treatment led to a strong inhibition of angiogenesis and an enhanced vessel maturation phenotype. Neoadjuvant combination with chemotherapy resulted in complete tumor regression in primary tumor-bearing Ang-2-VEGF-A CrossMab-treated mice. In contrast to Ang-1 inhibition, anti-Ang-2-VEGF-A treatment did not aggravate the adverse effect of anti-VEGF treatment on physiologic vessels. Moreover, treatment with Ang-2-VEGF-A CrossMab resulted in inhibition of hematogenous spread of tumor cells to other organs and reduced micrometastatic growth in the adjuvant setting.These data establish Ang-2-VEGF-A CrossMab as a promising antitumor, antiangiogenic, and antimetastatic agent for the treatment of cancer.
Early Results: “ROCKET” a phase II Study of RRx-001, a novel triple epigenetic inhibitor, Resensitization to Irinotecan in Colorectal Cancer
Authors: C. Carter, T. Reid, G. Fisher, C. Cho-Phan, P. Kunz, H. Kaiser, B. Oronsky, G. Fanger, S. Caroen, C. Parker, J. Scicinski
Journal: Annals of Oncology (2015)
Use and abuse of hydrogen breath tests
Authors: M Simren
Journal: Gut (2006)

Hydrogen breath tests are widely used to explore the pathophysiology of functional gastrointestinal disorders. Small intestinal bacterial overgrowth and carbohydrate malabsorption are disorders detected by these tests that have been proposed to be of great importance for symptoms in, for instance, irritable bowel syndrome. However, conclusions drawn from these studies are highly controversial and divergent results exist. There is also an extensive use of these tests in clinical practice with difficulties regarding interpretation of the tests and sometimes erroneous conclusions. The limitations and pitfalls of these tests will be reviewed in this article, and hopefully the occasional abuse of these tests can be turned into proper clinical and scientific use instead in the future.
Evaluation of Diabetic Foot Ulcer Healing With Hyperspectral Imaging of Oxyhemoglobin and Deoxyhemoglobin
Authors: Aksone Nouvong, Byron Hoogwerf, Emile Mohler, Brian Davis, Azita Tajaddini, Elizabeth Medenilla
Journal: Diabetes Care (2009)

OBJECTIVE Foot ulceration remains a major health problem for diabetic patients and has a major impact on the cost of diabetes treatment. We tested a hyperspectral imaging technology that quantifies cutaneous tissue hemoglobin oxygenation and generated anatomically relevant tissue oxygenation maps to assess the healing potential of diabetic foot ulcers (DFUs). RESEARCH DESIGN AND METHODS A prospective single-arm blinded study was completed in which 66 patients with type 1 and type 2 diabetes were enrolled and followed over a 24-week period. Clinical, medical, and diabetes histories were collected. Transcutaneous oxygen tension was measured at the ankles. Superficial tissue oxyhemoglobin (oxy) and deoxyhemoglobin (deoxy) were measured with hyperspectral imaging from intact tissue bordering the ulcer. A healing index derived from oxy and deoxy values was used to assess the potential for healing. RESULTS Fifty-four patients with 73 ulcers completed the study; at 24 weeks, 54 ulcers healed while 19 ulcers did not heal. When using the healing index to predict healing, the sensitivity was 80% (43 of 54), the specificity was 74% (14 of 19), and the positive predictive value was 90% (43 of 48). The sensitivity, specificity, and positive predictive values increased to 86, 88, and 96%, respectively, when removing three false-positive osteomyelitis cases and four false-negative cases due to measurements on a callus. The results indicate that cutaneous tissue oxygenation correlates with wound healing in diabetic patients. CONCLUSIONS Hyperspectral imaging of tissue oxy and deoxy may predict the healing of DFUs with high sensitivity and specificity based on information obtained from a single visit.
Body-Mass Index and Progression of Hepatitis B: A Population-Based Cohort Study in Men
Authors: Ming-Whei Yu, Wei-Liang Shih, Chih-Lin Lin, Chun-Jen Liu, Jhih-Wei Jian, Keh-Sung Tsai, Chien-Jen Chen
Journal: Journal of Clinical Oncology (2008)

Purpose To determine prospectively whether body-mass index (BMI) is associated with liver-related morbidity and mortality among male hepatitis B virus (HBV) carriers. Patients and Methods We performed a prospective study of 2,903 male HBV surface antigen–positive government employees who were free of cancer at enrollment between 1989 and 1992. Main outcome measures included ultrasonography, biochemical tests, incident hepatocellular carcinoma (HCC), and liver-related death. Results During mean follow-up of 14.7 years, 134 developed HCC and 92 died as a result of liver-related causes. In Cox proportional hazards models adjusting for age, number of visits, diabetes, and use of alcohol and tobacco, the hazard ratios for incident HCC were 1.48 (95% CI, 1.04 to 2.12) in overweight men (BMI between 25.0 and 29.9 kg/m 2 ) and 1.96 (95% CI, 0.72 to 5.38) in obese men (BMI ≥ 30.0 kg/m 2 ), compared with normal-weight men (BMI between 18.5 and 24.9 kg/m 2 ). Liver-related mortality had adjusted hazard ratios of 1.74 (95% CI, 1.15 to 2.65) in overweight men and 1.50 (95% CI, 0.36 to 6.19) in obese men. Excess BMI was also associated with the occurrence of fatty liver and cirrhosis detected by ultrasonography, as well as elevated ALT and γ-glutamyltransferase (GGT) activity during follow-up. The association of BMI with GGT was stronger than with ALT, and elevated GGT activity and cirrhosis were the strongest predictors for incident HCC and liver-related death. Conclusion This longitudinal cohort study indicates that excess body weight is involved in the transition from healthy HBV carrier state to HCC and liver-related death among men.