tbuckley/cabot-search huggingface dataset:
Antifungal Therapy with Itraconazole Impairs the Anti-Lymphoma Effects of Rituximab by Inhibiting Recruitment of CD20 to Cell Surface Lipid Rafts
Authors: Ingo Ringshausen, Yvonne Feuerstacke, Philipp Krainz, Jürgen den Hollander, Ken Hermann, Andreas Buck, Christian Peschel, Christian Meyer zum Bueschenfelde
Journal: Cancer Research (2010)

Immunotherapy with rituximab alone or in conjunction with chemotherapy has significantly improved the treatment outcome of B-cell lymphoma patients. Nevertheless, a subpopulation of patients does not respond to rituximab. The reason for treatment failure as well as the exact mechanism of action is still uncertain. The function of rituximab has long been associated with the partitioning of CD20 molecules to membrane microdomains. Here, we show that concomitant antifungal treatment with itraconazole impairs the rituximab anti-lymphoma effect both in vitro and in vivo. At the molecular level, recruitment of CD20 to lipid rafts is inhibited in the presence of itraconazole. Furthermore, calcium influx, which is crucial for rituximab-mediated cell death, was nearly completely abolished by itraconazole treatment. In contrast, the antifungal drug caspofungin did not inhibit CD20 recruitment to lipid rafts, nor did it affect calcium influx or the cytotoxic effect of rituximab. The finding that itraconazole also abolished the cytotoxic effects of other therapeutic antibodies directed against lipid raft-associated molecules (i.e., CD20 and CD52) but not those against the non-raft-associated molecule CD33 further supported our proposed mechanism of action. Our results argue that concomitant medications must be adjusted carefully to achieve optimal antitumor effects with monoclonal antibodies.
ELECTRIC SHOCK TREATMENT IN GENERAL PARESIS
Authors: GERT HEILBRUNN, PAUL FELDMAN
Journal: American Journal of Psychiatry (1943)

Electric shock therapy proved to be a perilous procedure in patients diagnosed psychosis with syphilitic meningo-encephalitis. Alarming cardiovascular and respiratory failure accompanying a major reaction or even a minimum reaction necessitated discontinuance of this kind of therapy before any clinical improvement was noticeable. Therefore, no evaluation regarding therapeutic benefit can be ventured. Two factors were discussed that may be responsible for the severe complications.
STUDIES ON CHARACTERIZATION OF THE LYMPHOID TARGET CELL FOR ACTIVITY OF A THYMUS HUMORAL FACTOR
Authors: Varda Rotter, Amiela Globerson, Ichiro Nakamura, Nathan Trainin
Journal: The Journal of Experimental Medicine (1973)

The immune response to SRBC was measured in the spleens of adult thymectomized, total body irradiated mice injected with various combinations of thymus and bone marrow cells together with thymic humoral factor (THF). It was found that the number of plaque-forming cells was significantly increased when THF was given in vivo immediately after thymus cell administration or when thymus cells were incubated in THF before injection. On the other hand, bone marrow cells equally treated did not manifest any T cell activity, since THF-treated bone marrow cells were not able to substitute thymus cells in the system used. The results accumulated in the present experiments indicate, therefore, that the target cells for THF activity are thymus cells which acquire a higher T helper cell capacity after THF treatment.
Beneficial Cardiovascular Pleiotropic Effects of Statins
Authors: Jean Davignon
Journal: Circulation (2004)

Pleiotropic effects of a drug are actions other than those for which the agent was specifically developed. These effects may be related or unrelated to the primary mechanism of action of the drug, and they are usually unanticipated. Pleiotropic effects may be undesirable (such as side effects or toxicity), neutral, or, as is especially the case with HMG-CoA reductase inhibitors (statins), beneficial. Pleiotropic effects of statins include improvement of endothelial dysfunction, increased nitric oxide bioavailability, antioxidant properties, inhibition of inflammatory responses, and stabilization of atherosclerotic plaques. These and several other emergent properties could act in concert with the potent low-density lipoprotein cholesterol-lowering effects of statins to exert early as well as lasting cardiovascular protective effects. Understanding the pleiotropic effects of statins is important to optimize their use in treatment and prevention of cardiovascular disease.
THE RELATION OF EXTROVERSION-INTROVERSION TO INTELLIGENCE AND TUBERCULOSIS
Authors: Clarence A. Neymann
Journal: American Journal of Psychiatry (1930)

1. Nine hundred normal individuals have been examined by the Neymann-Kohlstedt test. 2. Most individuals fall into one of the two groups, the introverts and the extroverts. 3. Intelligence and introversion do not coincide. 4. The average tuberculosis patient has a strong leaning toward introvertive qualities. 5. The introvertive qualities decrease as pulmonary tuberculosis becomes progressive and the patient becomes bed-ridden.
Comparison of staining methods in collagenous colitis
Authors: F O Dakhil
Journal: Gut (2009)

I read with interest the recent article by Pardi1 on collagenous colitis. In spite of the increased awareness of this condition among clinicians and pathologists, collagenous colitis, described by Lindstrom2 in 1976 and characterised by a thick subepithelial collagen band3 (>10 μm), is still underdiagnosed in many parts of the world. This is partly due to different diagnostic criteria and to the fact that the lower border of the band is not well demarcated. Therefore, correct estimation of the thickness of this band is not always reliable.

To compare the efficacy of the different staining methods used in measuring the thickness of the collagen layer in collagenous enterocolitis, including tenascin expression,4 we examined histological sections of 245 endoscopic biopsies from 199 symptomatic patients (140 female and 59 male) referred to the endoscopy unit …
Randomized Trial of an Allogeneic Melanoma Lysate Vaccine With Low-Dose Interferon Alfa-2b Compared With High-Dose Interferon Alfa-2b for Resected Stage III Cutaneous Melanoma
Authors: Malcolm S. Mitchell, Judith Abrams, John A. Thompson, Mohammed Kashani-Sabet, Ronald C. DeConti, Wen-Jen Hwu, Michael B. Atkins, Eric Whitman, Marc S. Ernstoff, Frank G. Haluska, James G. Jakowatz, Tapas K. Das Gupta, Jon M. Richards, Wolfram E. Samlowski, John J. Costanzi, Frederick R. Aronson, Albert B. Deisseroth, Arkadiusz Z. Dudek, Vicky E. Jones
Journal: Journal of Clinical Oncology (2007)

Purpose To compare the overall survival (OS) of patients with resected stage III melanoma administered active specific immunotherapy and low-dose interferon alfa-2b (IFN-α-2b) with the OS achieved using high-dose IFN-α-2b. Patients and Methods An Ad Hoc Melanoma Working Group of 25 investigators treated 604 patients from April 1997 to January 2003. Patients were stratified by sex and number of nodes and were randomly assigned to receive either 2 years of treatment with active specific immunotherapy with allogeneic melanoma lysates and low-dose IFN-α-2b (arm 1) or high-dose IFN-α-2b alone for 1 year (arm 2). Active specific immunotherapy was injected subcutaneously (SC) weekly for 4 weeks, at week 8, and bimonthly thereafter. IFN-α-2b SC was begun on week 4 and continued thrice weekly at 5 MU/m 2 for 2 years. IFN-α-2b in arm 2 was administered according to the Eastern Cooperative Oncology Group 1684 study regimen. Results Median follow-up time was 32 months for all patients and 42 months for surviving patients. Median OS time exceeds 84 months in arm 1 and is 83 months in arm 2 (P = .56). Five-year OS rate is 61% in arm 1 and 57% in arm 2. Estimated 5-year relapse-free survival (RFS) rate is 50% in arm 1 and 48% in arm 2, with median RFS times of 58 and 50 months, respectively. The incidence of serious adverse events as a result of treatment was the same in both arms, but more severe neuropsychiatric toxicity was seen in arm 2. Conclusion OS and RFS achieved by active specific immunotherapy and low-dose IFN-α-2b were indistinguishable from those achieved by high-dose IFN-α-2b. Long RFS and OS times were observed in both treatment arms.
Number and Migratory Activity of Circulating Endothelial Progenitor Cells Inversely Correlate With Risk Factors for Coronary Artery Disease
Authors: Mariuca Vasa, Stephan Fichtlscherer, Alexandra Aicher, Klaudia Adler, Carmen Urbich, Hans Martin, Andreas M. Zeiher, Stefanie Dimmeler
Journal: Circulation Research (2001)

Abstract —Recent studies provide increasing evidence that postnatal neovascularization involves bone marrow–derived circulating endothelial progenitor cells (EPCs). The regulation of EPCs in patients with coronary artery disease (CAD) is unclear at present. Therefore, we determined the number and functional activity of EPCs in 45 patients with CAD and 15 healthy volunteers. The numbers of isolated EPCs and circulating CD34/kinase insert domain receptor (KDR)-positive precursor cells were significantly reduced in patients with CAD by ≈40% and 48%, respectively. To determine the influence of atherosclerotic risk factors, a risk factor score including age, sex, hypertension, diabetes, smoking, positive family history of CAD, and LDL cholesterol levels was used. The number of risk factors was significantly correlated with a reduction of EPC levels ( R =−0.394, P =0.002) and CD34-/KDR-positive cells ( R =−0.537, P &lt;0.001). Analysis of the individual risk factors demonstrated that smokers had significantly reduced levels of EPCs ( P &lt;0.001) and CD34-/KDR-positive cells ( P =0.003). Moreover, a positive family history of CAD was associated with reduced CD34-/KDR-positive cells ( P =0.011). Most importantly, EPCs isolated from patients with CAD also revealed an impaired migratory response, which was inversely correlated with the number of risk factors ( R =−0.484, P =0.002). By multivariate analysis, hypertension was identified as a major independent predictor for impaired EPC migration ( P =0.043). The present study demonstrates that patients with CAD revealed reduced levels and functional impairment of EPCs, which correlated with risk factors for CAD. Given the important role of EPCs for neovascularization of ischemic tissue, the decrease of EPC numbers and activity may contribute to impaired vascularization in patients with CAD. The full text of this article is available at http://www.circresaha.org.
Free radicals and reperfusion arrhythmias. Commentaries on this month's Controversy articles From Morris Karmazyn and Margaret P Moffat
Authors: M. Karmazyn, M. P Moffat
Journal: Cardiovascular Research (1994)

Journal Article Free radicals and reperfusion arrhythmias. Commentaries on this month's Controversy articles From Morris Karmazyn and Margaret P Moffat Get access Morris Karmazyn, Morris Karmazyn Department of Pharmacology and Toxicology, University of Western Ontario, London, Ontario N6A 5C1, Canada. Search for other works by this author on: Oxford Academic PubMed Google Scholar Margaret P Moffat Margaret P Moffat Department of Pharmacology and Toxicology, University of Western Ontario, London, Ontario N6A 5C1, Canada. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 3, March 1994, Pages 426–427, https://doi.org/10.1093/cvr/28.3.426b Published: 01 March 1994
ENDOCRINE TUMORS OF THE GASTROINTESTINAL TRACT
Authors: Roger R. Perry, Aaron I. Vinik
Journal: Annual Review of Medicine (1996)

Endocrine tumors of the gastrointestinal tract produce a variety of secretory products that cause unique clinical syndromes. Diagnosis, which is often delayed, requires a strong index of suspicion and must be confirmed by biochemical tests. Precisely where these tumors originate remains a topic of controversy. However, several growth factors that may be involved in tumor development have been identified, and genetic abnormalities in patients with multiple endocrine neoplasia have been described. New pre- and intraoperative localization techniques have greatly increased the ability to identify and resect these tumors. The long-acting somatostatin analogue octreotide is frequently useful as a tracer to localize tumors and as symptomatic therapy for limiting release of secretory products produced by the tumors. In some instances it may also have direct anti-tumor activity.
Real-Time 3D Echocardiographic Quantification of Left Atrial Volume
Authors: Victor Mor-Avi, Chattanong Yodwut, Carly Jenkins, Harald Kühl, Hans-Joachim Nesser, Thomas H. Marwick, Andreas Franke, Lynn Weinert, Johannes Niel, Regina Steringer-Mascherbauer, Benjamin H. Freed, Lissa Sugeng, Roberto M. Lang
Journal: JACC. Cardiovascular imaging (2012)
Products of the IgT-C region of chromosome 12 are maturational markers for T cells. Sequence of appearance in immunocompetent T cells parallels ontogenetic appearance of Tthyd, Tindd, and Tsud.
Authors: F L Owen
Journal: The Journal of Experimental Medicine (1982)

Monoclonal antibodies specific for three T cell alloantigens linked to the immunoglobulin complex on chromosome 12 were used to establish the order of expression of these antigens on immunocompetent cells and in ontogeny. Modification of monoclonal antibodies with fluorescein isothiocyanate (FITC) and use with anti-FITC and complement has amplified lytic capacity of the monoclonals and allowed us to complete a distribution study of Tsud, Tindd, And Tthyd alloantigens on immunocompetent cells. Tthyd is expressed on both cortisone-sensitive and cortisone-resistant thymocytes; Tsud and Tindd are on "mature" cortisone-resistant cells. Tthyd is also expressed on a Thy-1.2-bearing recirculating marrow cell but is undetectable in the peripheral T cell pool. In contrast, resting spleen and lymph node T cells express Tsud and Tindd; antigen-activated populations express these two cells in high frequencies. These antigens must be markers for relatively differentiated cells because "nude" animals, which have pre-T cells, fail to express these determinants. All three antigens segregate independently in our T cell hybrids, arising from adult peripheral node cells, supporting the hypothesis that these are three separate structural products of a gene complex. In contrast, fetal T cell hybrids fail to express these antigens. The appearance of all three antigens on the cell surface in ontogeny is postnatal; Tthyd is expressed at days 1-2, Tindd at days 2-3, and Tsud at days 5-6. If the T cell isotype genes are organized similar to the immunoglobulin loci, then the parallels in maturational expression on immunocompetent cells and in ontogeny would lead one to speculate a gene order of Tthyd leads to Tindd leads to Tsud. Orientation with respect to the centromere is unknown.
Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial
Authors: F. Vadillo-Ortega, O. Perichart-Perera, S. Espino, M. A. Avila-Vergara, I. Ibarra, R. Ahued, M. Godines, S. Parry, G. Macones, J. F. Strauss
Journal: BMJ (2011)

<b>Objective</b> To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk. <b>Design</b> Randomised, blinded, placebo controlled clinical trial. <b>Setting</b> Tertiary public hospital in Mexico City. <b>Participants</b> Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery. <b>Interventions</b> Supplementation with a medical food—bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo—during pregnancy. <b>Main outcome measure</b> Development of pre-eclampsia/eclampsia. <b>Results</b> 222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (χ<sup>2</sup>=19.41; P&lt;0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (χ<sup>2</sup>=3.76; P=0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P=0.004; absolute risk reduction 0.09, 0.05 to 0.14). <b>Conclusions</b> Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be evaluated in a low risk population to determine the generalisability of the protective effect, and the relative contributions of L-arginine and antioxidant vitamins to the observed effects of the combined treatment need to be determined. <b>Trial registration</b> Clinical trials NCT00469846.
Elevated C-Reactive Protein Levels in Overweight and Obese Adults
Authors: Marjolein Visser
Journal: JAMA (1999)

Human adipose tissue expresses and releases the proinflammatory cytokine interleukin 6, potentially inducing low-grade systemic inflammation in persons with excess body fat.To test whether overweight and obesity are associated with low-grade systemic inflammation as measured by serum C-reactive protein (CRP) level.The Third National Health and Nutrition Examination Survey, representative of the US population from 1988 to 1994.A total of 16616 men and nonpregnant women aged 17 years or older.Elevated CRP level of 0.22 mg/dL or more and a more stringent clinically raised CRP level of more than 1.00 mg/dL.Elevated CRP levels and clinically raised CRP levels were present in 27.6% and 6.7% of the population, respectively. Both overweight (body mass index [BMI], 25-29.9 kg/m2) and obese (BMI, > or =30 kg/m2) persons were more likely to have elevated CRP levels than their normal-weight counterparts (BMI, <25 kg/m2). After adjustment for potential confounders, including smoking and health status, the odds ratio (OR) for elevated CRP was 2.13 (95% confidence interval [CI], 1.56-2.91) for obese men and 6.21 (95% CI, 4.94-7.81) for obese women. In addition, BMI was associated with clinically raised CRP levels in women, with an OR of 4.76 (95% CI, 3.42-6.61) for obese women. Waist-to-hip ratio was positively associated with both elevated and clinically raised CRP levels, independent of BMI. Restricting the analyses to young adults (aged 17-39 years) and excluding smokers, persons with inflammatory disease, cardiovascular disease, or diabetes mellitus and estrogen users did not change the main findings.Higher BMI is associated with higher CRP concentrations, even among young adults aged 17 to 39 years. These findings suggest a state of low-grade systemic inflammation in overweight and obese persons.
Clonality Analysis of Synchronous Lesions of Cervical Carcinoma Based on X Chromosome Inactivation Polymorphism, Human Papillomavirus Type 16 Genome Mutations, and Loss of Heterozygosity
Authors: Xinrong Hu, Tianyun Pang, Anna Asplund, Jan Pontén, Monica Nistér
Journal: The Journal of Experimental Medicine (2002)

One of the most common forms of carcinoma in women, cervical invasive squamous cell carcinoma (CIC), often coexists with multiple lesions of cervical intraepithelial neoplasia (CIN). CIC and CIN show heterogeneity with respect to both histopathology and biology. To understand the causes, origin, and model of progression of cervical carcinoma, we assessed the clonality of a case with multiple synchronous lesions by analyzing X chromosome inactivation polymorphism, human papillomavirus type 16 (HPV16) sequence variation/mutations, and loss of heterozygosity (LOH). Microdissection was performed on 24 samples from this case, representing the entire lesional situation. The combination of different X chromosome inactivation patterns, two HPV16 point mutations, and LOH at three genomic microsatellite loci, led to the identification of five different “monoclonal” lesions (CIN II, CIN III, and invasive carcinoma nests) and five different “polyclonal” areas (CIN II and normal squamous epithelium). This finding indicated that CIC can originate from multiple precursor cells, from which some clones might progress via multiple steps, namely via CIN II and CIN III, whereas others might develop independently and possibly directly from the carcinoma precursor cells. Our results also supported the view that HPV16 as a “field factor” causes cervical carcinoma, which is probably promoted by the loss of chromosomal material as indicated by the LOH.
Hepatitis C virus mutation affects proteasomal epitope processing
Authors: Ulrike Seifert, Heike Liermann, Vito Racanelli, Anne Halenius, Manfred Wiese, Heiner Wedemeyer, Thomas Ruppert, Kay Rispeter, Peter Henklein, Alice Sijts, Hartmut Hengel, Peter-M. Kloetzel, Barbara Rehermann
Journal: Journal of Clinical Investigation (2004)

The high incidence of hepatitis C virus (HCV) persistence raises the question of how HCV interferes with host immune responses. Studying a single-source HCV outbreak, we identified an HCV mutation that impaired correct carboxyterminal cleavage of an immunodominant HLA-A2–restricted CD8 cell epitope that is frequently recognized by recovered patients. The mutation, a conservative HCV nonstructural protein 3 (NS3) tyrosine to phenylalanine substitution, was absent in 54 clones of the infectious source, but present in 15/21 (71%) HLA-A2–positive and in 11/24 (46%) HLA-A2–negative patients with chronic hepatitis C. In order to analyze whether the mutation affected the processing of the HLA-A2–restricted CD8 cell epitope, mutant and wild-type NS3 polypeptides were digested in vitro with 20S constitutive proteasomes and with immunoproteasomes. The presence of the mutation resulted in impaired carboxyterminal cleavage of the epitope. In order to analyze whether impaired epitope processing affected T cell priming in vivo, HLA-A2–transgenic mice were infected with vaccinia viruses encoding either wild-type or mutant HCV NS3. The mutant induced fewer epitope-specific, IFN-γ;–producing and fewer tetramer+ cells than the wild type. These data demonstrate how a conservative mutation in the flanking region of an HCV epitope impairs the induction of epitope-specific CD8+ T cells and reveal a mechanism that may contribute to viral sequence evolution in infected patients.