tbuckley/cabot-search huggingface dataset:
The mechanism of anti-CD20–mediated B cell depletion revealed by intravital imaging
Authors: Fabricio Montalvao, Zacarias Garcia, Susanna Celli, Béatrice Breart, Jacques Deguine, Nico Van Rooijen, Philippe Bousso
Journal: Journal of Clinical Investigation (2013)

Anti-CD20 Ab therapy has proven successful for treating B cell malignancies and a number of autoimmune diseases. However, how anti-CD20 Abs operate in vivo to mediate B cell depletion is not fully understood. In particular, the anatomical location, the type of effector cells, and the mechanism underlying anti-CD20 therapy remain uncertain. Here, we found that the liver is a major site for B cell depletion and that recirculation accounts for the decrease in B cell numbers observed in secondary lymphoid organs. Using intravital imaging, we established that, upon anti-CD20 treatment, Kupffer cells (KCs) mediate the abrupt arrest and subsequent engulfment of B cells circulating in the liver sinusoids. KCs were also effective in depleting malignant B cells in a model of spontaneous lymphoma. Our results identify Ab-dependent cellular phagocytosis by KCs as a primary mechanism of anti-CD20 therapy and provide an experimental framework for optimizing the efficacy of therapeutic Abs.
Cross-Cultural Psychotherapy
Authors: WILLIAM M. BOLMAN
Journal: American Journal of Psychiatry (1968)

One of the major obstacles in the development of mental health services in large areas of the non-Western world is the difficulty in making culture- and language-specific adaptations of Western scientific approaches. Individual psychotherapy is a powerful tool in the generation of such culture-specific concepts; it can be a highly useful technique for transcultural psychiatry. Toward this goal the author proposes a basic model which involves two therapists, one representing each culture, together with additional consultation depending upon their degree of cultural "fit."
The Glu298-Asp endothelial nitric oxide synthase gene polymorphism interacts with environmental and dietary factors to influence endothelial function
Authors: C P Leeson, A D Hingorani, M J Mullen, N Jeerooburkhan, M Kattenhorn, D P Muller, A Lucas, S E Humphries, J E Deanfield
Journal: Circulation (2000)
Anti-CD4 monoclonal antibody treatment in acute and early chronic antigen induced arthritis: influence on macrophage activation
Authors: K Nissler
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To investigate the indirect effects of anti-CD4 treatment on the functions of macrophages (CD4<sup>−</sup> in mice) in the acute and early chronic phase of mouse antigen induced arthritis (AIA). <b>Methods:</b> C57BL/6 mice with AIA were treated intraperitoneally with the anti-CD4 mAb GK1.5 or control rat IgG on days −1, 0, 1, 3, 5, and 7. Proinflammatory cytokines (IL1β, IL6, and TNFα) were quantified by sandwich ELISA in joint extracts, serum, and supernatants of ex vivo stimulated spleen/lymph node cells or peritoneal macrophages (+LPS/IFNγ). Nitric oxide (NO) levels in supernatants of ex vivo stimulated peritoneal macrophages were measured by the Griess reaction. Proteolytic activity in joint homogenates was analysed by gelatin, casein, and elastin zymography, and substrate assays. <b>Results:</b> Anti-CD4 treatment significantly reduced joint swelling in acute (days 3, 5) and early chronic AIA (day 7) and diminished inflammation and destruction scores in late chronic AIA (day 21). On day 3, anti-CD4 treatment significantly reduced IL6 levels in all compartments. IL1β was reduced in joint extracts, unaffected in serum or cells from lymphoid organs, and increased in stimulated peritoneal macrophages. TNFα was significantly increased in the joints, decreased in serum, and otherwise unchanged. NO production by stimulated peritoneal macrophages was significantly reduced by anti-CD4 treatment. Lower activity of matrix metalloproteinases and neutrophil elastase was seen in joint extracts of anti-CD4 treated animals than in IgG treated AIA controls. <b>Conclusion:</b> CD4<sup>+</sup> T cell directed treatment had strong local and systemic effects on macrophages. These indirect effects may contribute to the reduction of destructive mediators/joint destruction in AIA.
ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias∗∗This document does not cover atrial fibrillation; atrial fibrillation is covered in the ACC/AHA/ESC guidelines on the management of patients with atrial fibrillation found on the ACC, AHA, and ESC Web sites.—executive summary
Authors: Carina Blomström-Lundqvist, Melvin M Scheinman, Etienne M Aliot, Joseph S Alpert, Hugh Calkins, A.John Camm, W.Barton Campbell, David E Haines, Karl H Kuck, Bruce B Lerman, D.Douglas Miller, Charlie Willard Shaeffer, William G Stevenson, Gordon F Tomaselli, Elliott M Antman, Sidney C Smith, Joseph S Alpert, David P Faxon, Valentin Fuster, Raymond J Gibbons, Gabriel Gregoratos, Loren F Hiratzka, Sharon Ann Hunt, Alice K Jacobs, Richard O Russell, Silvia G Priori, Jean-Jacques Blanc, Andzrej Budaj, Enrique Fernandez Burgos, Martin Cowie, Jaap Willem Deckers, Maria Angeles Alonso Garcia, Werner W Klein, John Lekakis, Bertil Lindahl, Gianfranco Mazzotta, João Carlos Araujo Morais, Ali Oto, Otto Smiseth, Hans-Joachim Trappe
Journal: Journal of the American College of Cardiology (2003)
Uterine Leiomyomata with t(10;17) Disrupt the Histone Acetyltransferase <b> <i>MORF</i> </b>
Authors: Steven D. P. Moore, Steven R. Herrick, Tan A. Ince, Michael S. Kleinman, Paola Dal Cin, Cynthia C. Morton, Bradley J. Quade
Journal: Cancer Research (2004)

Abstract Benign uterine leiomyomata are the most common tumors in women of reproductive age. One recurring chromosomal aberration in uterine leiomyomata is rearrangement of 10q22. Chromosome 10 breakpoints were mapped by fluorescence in situ hybridization to intervals ranging from 8.9 to 72.1 kb within the third intron of MORF (monocytic leukemia zinc finger protein-related factor or MYST4) in four uterine leiomyomata tested. Additional Southern hybridization experiments confirmed that the breakpoint lies within the third intron and narrowed the interval to 2.1 kb in one uterine leiomyomata. MORF is a member of the MYST family of histone acetyltransferase and previously has been found rearranged in some types of acute myeloid leukemia (AML). This is the first instance in which disruption of a histone acetyltransferase has been reported in another tumor type. The breakpoints in uterine leiomyomata would fall in the NH2-terminal portion of the protein between a conserved domain found in histones H1 and H5 and the PHD zinc fingers, the CH2CH zinc finger, or the CoA binding site, which is distinct from the breakpoints reported in AML. Mapping of the 17q21 breakpoint by fluorescence in situ hybridization within a specific region in three tumors revealed several positional candidates including GCN5L2, a gene with histone acetyltransferase activity similar to those fused to MORF in AML. Of note, two of three uterine leiomyomata were of the cellular subtype. Involvement of MORF in four uterine leiomyomata with chromosomal rearrangements involving 10q22 and 17q21 suggests a role for this histone acetyltransferase and altered chromatin regulation in uterine mesenchymal neoplasia.
Medullary Control of Vascular Resistance
Authors: VINCENT S. AAKI, MICHAEL J. BRODY
Journal: Circulation Research (1966)

Relationships between electrical activity in medullary vasomotor areas and reflex changes in peripheral vascular resistance were studied in dogs in which the hindquarters were autoperfused. Electrical stimulation through bipolar electrodes indicated a diffuse distribution of vasoactive points. Points yielding vasoconstrictor responses were found primarily in the rostral half of the medulla oblongata, while vasodilator points were located in the caudal and ventral portions of the medulla. Extensive crossing of vasomotor pathways was shown by the fact that stimulation of a single medullary point resulted in vascular resistance changes in both the ipsilateral and contralateral limbs. Stimulation of vasodilator points resulted in noncholinergic active vasodilatation in the hindlimb. The dilatation was considered to be active because it exceeded the sustained dilatation produced by lumbar sympathectomy and was reduced in magnitude by the antihistamine, ripelennamine. Discharge recorded through the electrodes from the same points which, when stimulated, gave vasomotor responses in the limb was larger in the vasoconstrictor point than in the vasodilator point. This difference may represent a central reflection of tonic sympathetic vasoconstrictor discharge. Reflex vasodilatation produced by intravenous norepinephrine was accompanied by a small but significant increase in activity recorded from vasodilator points. Other reflex stimuli, which included asphyxia and elevation and depression of carotid sinus pressure, elicited changes in electrical activity from the vasoconstrictor and vasodilator areas which, although small in magnitude, followed directions which were predicted on the basis of the existence of separate vasodilator and vasoconstrictor neurone pools. It was concluded that neurones exist in the medulla which probably play a role in exciting vasodilator pathways involved in reflex vasodilatation.
Community- and Individual-Level Socioeconomic Status and Breast Cancer Risk: Multilevel Modeling on Cape Cod, Massachusetts
Authors: Thomas F. Webster, Kate Hoffman, Janice Weinberg, Verónica Vieira, Ann Aschengrau
Journal: Environmental Health Perspectives (2008)

BackgroundPrevious research demonstrated increased risk of breast cancer associated with higher socioeconomic status (SES) measured at both the individual and community levels. However, little attention has been paid to simultaneously examining both measures.ObjectivesWe evaluated the independent influences of individual and community SES on the risk of breast cancer using case–control data. Because our previous work suggests that associations may be stronger after including a latency period, we also assessed the effect of community-level SES assuming a 10-year latency period.MethodsWe obtained individual education for cases and matched controls diagnosed between 1987 and 1993 on Cape Cod, Massachusetts (USA). We acquired community-level SES from census data for 1980 and 1990. Using SES data at diagnosis and 10 years earlier, we constructed models for breast cancer risk using individual-level SES only, community-level SES only, and a multilevel analysis including both. We adjusted models for other individual-level risk factors.ResultsWomen with the highest education were at greater risk of developing breast cancer in both 1980 and 1990 [odds ratio (OR) = 1.17 and 1.19, respectively]. Similarly, women living in the highest-SES communities in 1990 had greater risk (OR = 1.30). Results were stronger in the analyses considering a latency period (OR = 1.69). Adjusting for intragroup correlation had little effect on the analyses.ConclusionsModels including individual- or community-level measures of SES produced associations similar to those observed in previous research. Results for models including both measures are consistent with a contextual effect of SES on risk of breast cancer independent of individual SES.
Phase I and Pharmacokinetic Study of Pemetrexed Administered Every 3 Weeks to Advanced Cancer Patients With Normal and Impaired Renal Function
Authors: Alain C. Mita, Christopher J. Sweeney, Sharyn D. Baker, Andrew Goetz, Lisa A. Hammond, Amita Patnaik, Anthony W. Tolcher, Miguel Villalona-Calero, Alan Sandler, Tuhin Chaudhuri, Kathleen Molpus, Jane E. Latz, Lorinda Simms, Ajai K. Chaudhary, Robert D. Johnson, Eric K. Rowinsky, Chris H. Takimoto
Journal: Journal of Clinical Oncology (2006)

This phase I study was conducted to determine the toxicities, pharmacokinetics, and recommended doses of pemetrexed in cancer patients with normal and impaired renal function.Patients received a 10-minute infusion of 150 to 600 mg/m2 of pemetrexed every 3 weeks. Patients were stratified for independent dose escalation by measured glomerular filtration rate (GFR) into four cohorts ranging from > or = 80 to less than 20 mL/min. Pemetrexed plasma and urine pharmacokinetics were evaluated for the first cycle. Patients enrolled after December 1999 were supplemented with oral folic acid and intramuscular vitamin B12.Forty-seven patients were treated with 167 cycles of pemetrexed. Hematologic dose-limiting toxicities occurred in vitamin-supplemented patients (two; 15%) and non-supplemented patients (six; 18%), and included febrile neutropenia (four patients) and grade 4 thrombocytopenia (two patients). Nonhematologic toxicities included fatigue, diarrhea, and nausea, and did not correlate with renal function. Accrual was discontinued in patients with GFR less than 30 mL/min after one patient with a GFR of 19 mL/min died as a result of treatment-related toxicities. Pemetrexed plasma clearance positively correlated with GFR (r2 = 0.736), resulting in increased drug exposures in patients with impaired renal function. With vitamin supplementation, pemetrexed 600 mg/m2 was tolerated by patients with a GFR > or = 80 mL/min, whereas patients with a GFR of 40 to 79 mL/min tolerated a dose of 500 mg/m2.Pemetrexed was well tolerated at doses of 500 mg/m2 with vitamin supplementation in patients with GFR > or = 40 mL/min. Additional studies are needed to define appropriate dosing for renally impaired patients receiving higher dose pemetrexed with vitamin supplementation.
Outcome of treatment discontinuation in patients with metastatic renal cell carcinoma and no evidence of disease following targeted therapy with or without metastasectomy
Authors: M. Johannsen, M. Staehler, C.-H. Ohlmann, A. Flörcken, A. Schmittel, T. Otto, A. Bex, P. Hein, K. Miller, S. Weikert, V. Grünwald
Journal: Annals of Oncology (2010)
Risk of Pediatric Celiac Disease According to HLA Haplotype and Country
Authors: Edwin Liu, Hye-Seung Lee, Carin A. Aronsson, William A. Hagopian, Sibylle Koletzko, Marian J. Rewers, George S. Eisenbarth, Polly J. Bingley, Ezio Bonifacio, Ville Simell, Daniel Agardh
Journal: New England Journal of Medicine (2014)

The presence of HLA haplotype DR3–DQ2 or DR4–DQ8 is associated with an increased risk of celiac disease. In addition, nearly all children with celiac disease have serum antibodies against tissue transglutaminase (tTG).
Secrecy and Integrity in Clinical Trials
Authors: Robert J. Wells
Journal: Journal of Clinical Oncology (2008)

From the Division of Pediatrics, Chil-dren’s Cancer Hospital at The Univer-sity of Texas M.D. Anderson CancerCenter, Houston, TX.Submitted November 26, 2007;accepted December 3, 2007.Author’s disclosures of potential con-ﬂicts of interest and author contribu-tions are found at the end of thisarticle.Corresponding author: Robert J. Wells,MD, Pediatrics, The University of TexasM.D. Anderson Cancer Center, Unit 87,1515 Holcombe Blvd, Houston, TX77030; e-mail: rjwells@mdanderson.org.© 2008 by American Society of ClinicalOncology0732-183X/08/2604-680/$20.00DOI: 10.1200/JCO.2007.15.5234
Reduction of Major Adverse Cardiac Events With Intracoronary Compared With Intravenous Bolus Application of Abciximab in Patients With Acute Myocardial Infarction or Unstable Angina Undergoing Coronary Angioplasty
Authors: Jochen Wöhrle, Olaf C. Grebe, Thorsten Nusser, Eyas Al-Khayer, Stefan Schaible, Matthias Kochs, Vinzenz Hombach, Martin Höher
Journal: Circulation (2003)

Background— In patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty, abciximab reduces major adverse cardiac events (MACE). Clinical trials have studied intravenous administration only. Intracoronary bolus application of abciximab causes very high local drug concentrations and may be more effective. We studied whether intracoronary bolus administration of abciximab is associated with a reduced MACE rate compared with the standard intravenous bolus application. Methods and Results— We stratified 403 consecutive patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty according to the type of application of abciximab. A 20-mg bolus of abciximab was given intravenously in 109 patients and intracoronarily in 294 patients. There were no differences between the groups with regard to diabetes mellitus, cardiogenic shock, successful intervention, or preprocedural and postprocedural TIMI flow. At 30 days, the incidence of MACE (death, myocardial infarction, urgent revascularization) was significantly lower in the patients with intracoronary compared with intravenous administration of abciximab (10.2% versus 20.2%; P &lt;0.008), which was independent from stenting in multivariate analysis. The effect was most pronounced in patients with preprocedural TIMI 0/1 flow (MACE: intracoronary 11.8% versus intravenous 27.5%, P &lt;0.002; n=273). Conclusions— In patients with acute myocardial infarction or unstable angina undergoing emergency coronary angioplasty, intracoronary bolus application of abciximab is associated with a reduction of MACE compared with the standard intravenous bolus application of abciximab. Prospective, randomized trials are warranted to further assess intracoronary application of abciximab.
Adult T cell leukemia: a tale of two T cells
Authors: O. J. Semmes
Journal: Journal of Clinical Investigation (2006)

Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent for the development of an aggressive hematologic neoplasia termed adult T cell leukemia/lymphoma (ATLL). Although the virus infects T cell subsets that display either CD4 or CD8 cell surface markers, the leukemic cell is exclusively of the CD4+ subtype. In the article by Sibon et al. in this issue of the JCI, the authors demonstrate that the molecular basis for clonal expansion differs between these 2 infected T cell populations (see the related article beginning on page 974). The molecular events associated with a preleukemic state, such as genomic instability, polynucleation, and cell cycle redistribution, were only observed in CD4+ T cells. This finding provides a molecular-based mechanism for the restriction of the leukemic phenotype to the CD4+ T cell subtype.
In Vivo–Activated Cd4 T Cells Upregulate Cxc Chemokine Receptor 5 and Reprogram Their Response to Lymphoid Chemokines
Authors: K. Mark Ansel, Louise J. McHeyzer-Williams, Vu N. Ngo, Michael G. McHeyzer-Williams, Jason G. Cyster
Journal: The Journal of Experimental Medicine (1999)

Migration of antigen-activated CD4 T cells to B cell areas of lymphoid tissues is important for mounting T cell–dependent antibody responses. Here we show that CXC chemokine receptor (CXCR)5, the receptor for B lymphocyte chemoattractant (BLC), is upregulated on antigen-specific CD4 T cells in vivo when animals are immunized under conditions that promote T cell migration to follicles. In situ hybridization of secondary follicles for BLC showed high expression in mantle zones and low expression in germinal centers. When tested directly ex vivo, CXCR5hi T cells exhibited a vigorous chemotactic response to BLC. At the same time, the CXCR5hi cells showed reduced responsiveness to the T zone chemokines, Epstein-Barr virus–induced molecule 1 (EBI-1) ligand chemokine (ELC) and secondary lymphoid tissue chemokine (SLC). After adoptive transfer, CXCR5hi CD4 T cells did not migrate to follicles, indicating that additional changes may occur after immunization that help direct T cells to follicles. To further explore whether T cells could acquire an intrinsic ability to migrate to follicles, CD4−CD8− double negative (DN) T cells from MRL-lpr mice were studied. These T cells normally accumulate within follicles of MRL-lpr mice. Upon transfer to wild-type recipients, DN T cells migrated to follicle proximal regions in all secondary lymphoid tissues. Taken together, our findings indicate that reprogramming of responsiveness to constitutively expressed lymphoid tissue chemokines plays an important role in T cell migration to the B cell compartment of lymphoid tissues.
Non-steroidal anti-inflammatory drugs as a possible cause of collagenous colitis: a case-control study.
Authors: R H Riddell, M Tanaka, G Mazzoleni
Journal: Gut (1992)

The use of oral non-steroidal anti-inflammatory drugs (NSAIDs) in 31 patients with collagenous colitis and in 31 matched control patients with irritable bowel syndrome or colonic diverticular disease who had also undergone colonoscopy and biopsy was investigated. The long term use (greater than 6 months) of NSAIDs was significantly commoner in the study group (19/31) than in the control group (4/31) (p less than 0.02), even assuming the most adverse drug history in six patients in whom this could not be established. In all patients with collagenous colitis taking NSAIDs, diarrhoea followed the use of these drugs, and by a mean (SD) of 5.5 (4.4) years (range 0.5 to 15 years). In three patients with collagenous colitis, diarrhoea improved after withdrawing NSAIDs; rechallenge in one was followed by a recurrence of diarrhoea, which improved after withdrawing the drug again. It is suggested that NSAIDs may play an aetiological role in the diarrhoea and thickened collagen band in some patients with collagenous colitis.
Pkd1 regulates immortalized proliferation of renal tubular epithelial cells through p53 induction and JNK activation
Authors: Saori Nishio, Masahiko Hatano, Michio Nagata, Shigeo Horie, Takao Koike, Takeshi Tokuhisa, Toshio Mochizuki
Journal: Journal of Clinical Investigation (2005)

Autosomal dominant polycystic kidney disease (ADPKD) is the most common human monogenic genetic disorder and is characterized by progressive bilateral renal cysts and the development of renal insufficiency. The cystogenesis of ADPKD is believed to be a monoclonal proliferation of PKD-deficient (PKD–/–) renal tubular epithelial cells. To define the function of Pkd1, we generated chimeric mice by aggregation of Pkd1–/– ES cells and Pkd1+/+ morulae from ROSA26 mice. As occurs in humans with ADPKD, these mice developed cysts in the kidney, liver, and pancreas. Surprisingly, the cyst epithelia of the kidney were composed of both Pkd1–/– and Pkd1+/+ renal tubular epithelial cells in the early stages of cystogenesis. Pkd1–/– cyst epithelial cells changed in shape from cuboidal to flat and replaced Pkd1+/+ cyst epithelial cells lost by JNK-mediated apoptosis in intermediate stages. In late-stage cysts, Pkd1–/– cells continued immortalized proliferation with downregulation of p53. These results provide a novel understanding of the cystogenesis of ADPKD patients. Furthermore, immortalized proliferation without induction of p53 was frequently observed in 3T3-type culture of mouse embryonic fibroblasts from Pkd1–/– mice. Thus, Pkd1 plays a role in preventing immortalized proliferation of renal tubular epithelial cells through the induction of p53 and activation of JNK.