tbuckley/cabot-search huggingface dataset:
Positive Selection of γδ CTL by TL Antigen Expressed in the Thymus
Authors: Kunio Tsujimura, Toshitada Takahashi, Akimichi Morita, Hitomi Hasegawa-Nishiwaki, Shigeru Iwase, Yuichi Obata
Journal: The Journal of Experimental Medicine (1996)

To elucidate the function of the mouse TL antigen in the thymus, we have derived two TL transgenic mouse strains by introducing Tlaa-3 of A strain origin with its own promoter onto a C3H background with no expression of TL in the thymus. These transgenic mouse strains, both of which express high levels of Tlaa-3-TL antigen in their thymus, were analyzed for their T cell function with emphasis on cytotoxic T lymphocyte (CTL) generation. A T cell response against TL was induced in Tg.Tlaa-3-1, Tg.Tlaa-3-2, and control C3H mice by skin grafts from H-2Kb/T3b transgenic mice, Tg.Con.3-1, expressing T3b-TL ubiquitously. Spleen cells from mice that had rejected the T3b-TL positive skin grafts were restimulated in vitro with Tg.Con.3-1 irradiated spleen cells. In mixed lymphocyte cultures (MLC), approximately 20% and 15% of Thy-1+ T cells derived from Tg.Tlaa-3-1 and Tg.Tlaa-3-2, respectively, expressed TCRγδ, whereas almost all those from C3H expressed TCRαβ. The MLC from Tg.Tlaa-3-2 and C3H demonstrated high CTL activity against TL, while those from Tg.Tlaa-3-1 had little or none. The generation of γδ CTL recognizing TL in Tg.Tlaa-3-2, but not C3H mice, was confirmed by the establishment of CTL clones. A total of 14 γδ CTL clones were established from Tg.Tlaa-3-2, whereas none were obtained from C3H. Of the 14 γδ CTL clones, 8 were CD8+ and 6 were CD4−CD8− double negative. The CTL activity of all these clones was TL specific and inhibited by anti-TL, but not by anti-H-2 antibodies, demonstrating that they recognize TL directly without antigen presentation by H-2. The CTL activity was blocked by antibodies to TCRγδ and CD3, and also by antibodies to CD8α and CD8β in CD8+ clones, showing that the activity was mediated by TCRγδ and coreceptors. The thymic origin of these γδ CTL clones was indicated by the expression of Thy-1 and Ly-1 (CD5), and also CD8αβ heterodimers in CD8+ clones on their surfaces and by the usage of TCR Vγ4 chains in 12 of the 14 clones. Taken together, these results suggest that Tlaa-3-TL antigen expressed in the thymus engages in positive selection of a sizable population of γδ T cells.
AGR2 Is a Novel Surface Antigen That Promotes the Dissemination of Pancreatic Cancer Cells through Regulation of Cathepsins B and D
Authors: Laurent Dumartin, Hannah J. Whiteman, Mark E. Weeks, Deepak Hariharan, Branko Dmitrovic, Christine A. Iacobuzio-Donahue, Teresa A. Brentnall, Mary P. Bronner, Roger M. Feakins, John F. Timms, Caroline Brennan, Nicholas R. Lemoine, Tatjana Crnogorac-Jurcevic
Journal: Cancer Research (2011)

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers largely due to disseminated disease at the time of presentation. Here, we investigated the role and mechanism of action of the metastasis-associated protein anterior gradient 2 (AGR2) in the pathogenesis of pancreatic cancer. AGR2 was induced in all sporadic and familial pancreatic intraepithelial precursor lesions (PanIN), PDACs, circulating tumor cells, and metastases studied. Confocal microscopy and flow cytometric analyses indicated that AGR2 localized to the endoplasmic reticulum (ER) and the external surface of tumor cells. Furthermore, induction of AGR2 in tumor cells regulated the expression of several ER chaperones (PDI, CALU, RCN1), proteins of the ubiquitin-proteasome degradation pathway (HIP2, PSMB2, PSMA3, PSMC3, and PSMB4), and lysosomal proteases [cathepsin B (CTSB) and cathepsin D (CTSD)], in addition to promoting the secretion of the precursor form pro-CTSD. Importantly, the invasiveness of pancreatic cancer cells was proportional to the level of AGR2 expression. Functional downstream targets of the proinvasive activity of AGR2 included CTSB and CTSD in vitro, and AGR2, CTSB, and CTSD were essential for the dissemination of pancreatic cancer cells in vivo. Taken together, the results suggest that AGR2 promotes dissemination of pancreatic cancer and that its cell surface targeting may permit new strategies for early detection as well as therapeutic management.
Mechanism of Wenckebach A-V block and the obligatory ventricular echo
Authors: A. I. SCHAFFER, N. P. DEPASQUALE
Journal: Cardiovascular Research (1973)

Journal Article Mechanism of Wenckebach A-V block and the obligatory ventricular echo Get access ABRAHAM I. SCHAFFER, ABRAHAM I. SCHAFFER Department of Medicine Lenox Hill Hospital, 100 East 77 Street, New York, New York 10021, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar NICHOLAS P. DEPASQUALE NICHOLAS P. DEPASQUALE Department of Medicine Lenox Hill Hospital, 100 East 77 Street, New York, New York 10021, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 7, Issue 5, September 1973, Pages 696–702, https://doi.org/10.1093/cvr/7.5.696 Published: 01 September 1973
A rare cause of dysphagia
Authors: José M Conchillo, Michiel de Haan, Geert W H Schurink, Ad A M Masclee
Journal: Gut (2012)

A 54-year-old woman, with a history of partial strumectomy due to hyperthyroidism, was referred for evaluation of chronic dysphagia for solids for more than 10 years. In the last few months, she was only fed on a liquid diet and lost approximately 6 kg in weight. Neither reflux symptoms nor thoracic pain were present. Physical examination and screening blood tests were unremarkable. Upper endoscopy (supplementary video, figure 1), oesophageal high-resolution manometry (figure 2 …
Geographic distribution of hepatitis B virus (HBV) genotype in patients with chronic HBV infection in Japan
Authors: Etsuro Orito, Takafumi Ichida, Hiroshi Sakugawa, Michio Sata, Norio Horiike, Keisuke Hino, Kiwamu Okita, Takeshi Okanoue, Shiro Iino, Eiji Tanaka, Kazuyuki Suzuki, Hisayoshi Watanabe, Shuhei Hige, Masashi Mizokami
Journal: Hepatology (2001)

The geographic distribution of hepatitis B virus (HBV) genotypes in Japan and its clinical relevance are poorly understood. We studied 731 Japanese patients with chronic HBV infection. HBV genotype was determined by the restriction fragment length polymorphism (RFLP) method after polymerase chain reaction (PCR). Of the 720 patients with positive PCR, 12 (1.7%) were HBV genotype A, 88 (12.2%) were genotype B, 610 (84.7%) were genotype C, 3 (0.4%) were genotype D, and 7 (1.0%) were of mixed genotype. Over 94% of patients on the Japanese mainland had genotype C, while 60% of the patients on Okinawa, the most southern islands, and 22.9% in the Tohoku area, the northern part of the mainland, harbored genotype B. Compared with genotype C patients, genotype B patients were older (53.6 to 42.2 years; P &lt; .01), had a lower rate of positive hepatitis B e antigen (HBeAg) (18.4% to 50.6%; P &lt; .01), and a lower level of serum HBV DNA (5.02 to 5.87 log genome equivalents (LGE)/mL; P &lt; .01). The mean age of the genotype B patients with hepatocellular carcinoma was 70.1 ± 9.2 years, compared with 55.2 ± 9.7 of genotype C patients ( P &lt; .01). These results indicate that genotypes C and B are predominant in Japan, and there are significant differences in geographic distribution and clinical characteristics among the patients with the different genotypes. (Hepatology 2001;34:590-594.)
30 cases of tracheobronchopathia osteochondroplastica: Multicenter analysis
Authors: Seung Wook Jung, Yeon Jae Kim, Byung Ki Lee, Shin Yup Lee, Chi Young Jung, Kyung Chan Kim, Dae Sung Hyun
Journal: European Respiratory Journal (2011)

Background:  Tracheobronchopathia osteochondroplastica (TBO) is a rare benign disease characterized by multiple submucosal osteocartilaginous nodules of trachea and bronchi. However, data concerning TBO patients are limited in korea.   Methods:  From 2005 through 2010, a retrospective study was conducted in 30 TBO patients recruited from 4 hospitals (3 university faciliated hospitals and 1 community hospital) in korea. The baseline characteristics, clinical presentations, radiographic features, bronchoscopic findings and clinical outcomes in these patients were reviewed.   Results:  Among the 14,267 patients with flexible fiberoptic bronchoscopy, 30 patients (0.2%) were diagnosed with TBO. Patients were composed of 17 male and 13 female with a mean age of 60 years. The common symptoms were cough, dyspnea, and hemoptysis. Endotracheal nodules were the most common findig on computed tomography (CT). Osteocartilaginous nodules were mainly present in trachea on bronchoscopy, and the most common type was confluent form. The mean FEV1 was 101%predicted. Treatment included mostly conservative (n = 29) and then symptoms were considerably relieved in 8 cases but there was no significant improvement noted in 18 patients. 4 patients died on account of associated lung lesion.   Conclusion:  In accordance with previous studies, TBO is a rare disease and the diagnosis should be suspected based on CT findings and bronchoscopic examination of the airways. This study demonstrated that conservative treatment according to clinical symptom was effective and showed relatively good clinical outcome.
Frequency domain measures of heart rate variability before the onset of nonsustained and sustained ventricular tachycardia in patients with coronary artery disease.
Authors: H V Huikuri, J O Valkama, K E Airaksinen, T Seppänen, K M Kessler, J T Takkunen, R J Myerburg
Journal: Circulation (1993)

BACKGROUND Low heart rate variability (HRV) is associated with an increased risk of arrhythmic death and ventricular tachycardia (VT). The purpose of this study was to examine whether there is a temporal relation between changes in HRV and the onset of spontaneous episodes of VT in patients at high risk of life-threatening arrhythmias. METHODS AND RESULTS Components of HRV in the frequency domain were analyzed before the onset of 28 episodes of nonsustained VT (more than four impulses; duration &lt; 30 seconds) and 12 episodes of sustained VT (&gt; 30 seconds or requiring defibrillation) in 18 patients with coronary artery disease. Seven patients had survived cardiac arrest not associated with acute myocardial infarction, and 11 had a history of sustained VT. All frequency domain measures of HRV, i.e., total power (p &lt; 0.001), high-frequency power (p &lt; 0.05), low-frequency power (p &lt; 0.01), very-low-frequency power (p &lt; 0.01), and ultralow-frequency power (p &lt; 0.05), were significantly lower before the onset of sustained VT than before nonsustained VT. Total power of HRV was also lower during the 1-hour period before the onset of sustained VT than the average 24-hour HRV (p &lt; 0.05). An indirect correlation existed between the length of VT and the total power of HRV analyzed during the 15 minutes before the onset of VT (r = 0.54, p &lt; 0.01). HRV had a trend toward increasing values before the onset of nonsustained VT (p &lt; 0.01) but not before the sustained VT episodes. The ratio between low-frequency and high-frequency powers increased substantially before both nonsustained and sustained VT episodes (p = 0.06 and p = 0.05, respectively). The rate of VT or the coupling interval initiating the VT did not differ significantly between the nonsustained and sustained VT. CONCLUSIONS Spontaneous episodes of VT are preceded by changes in HRV in the frequency domain. Divergent dynamics of HRV before the onset of nonsustained and sustained VT episodes may reflect differences in factors that can facilitate the perpetuation of these arrhythmias.
Crystal Structure of the T315I Abl Mutant in Complex with the Aurora Kinases Inhibitor PHA-739358
Authors: Michele Modugno, Elena Casale, Chiara Soncini, Pamela Rosettani, Riccardo Colombo, Rosita Lupi, Luisa Rusconi, Daniele Fancelli, Patrizia Carpinelli, Alexander D. Cameron, Antonella Isacchi, Jürgen Moll
Journal: Cancer Research (2007)

Mutations in the kinase domain of Bcr-Abl are the most common cause of resistance to therapy with imatinib in patients with chronic myelogenous leukemia (CML). Second-generation Bcr-Abl inhibitors are able to overcome most imatinib-resistant mutants, with the exception of the frequent T315I substitution, which is emerging as a major cause of resistance to these drugs in CML patients. Structural studies could be used to support the drug design process for the development of inhibitors able to target the T315I substitution, but until now no crystal structure of the T315I Abl mutant has been solved. We show here the first crystal structure of the kinase domain of Abl T315I in complex with PHA-739358, an Aurora kinase inhibitor currently in clinical development for solid and hematologic malignancies. This compound inhibits in vitro the kinase activity of wild-type Abl and of several mutants, including T315I. The cocrystal structure of T315I Abl kinase domain provides the structural basis for this activity: the inhibitor associates with an active conformation of the kinase domain in the ATP-binding pocket and lacks the steric hindrance imposed by the substitution of threonine by isoleucine.
Familial Alzheimer's Disease–Linked Presenilin 1 Variants Elevate Aβ1–42/1–40 Ratio In Vitro and In Vivo
Authors: David R. Borchelt, Gopal Thinakaran, Christopher B. Eckman, Michael K. Lee, Frances Davenport, Tamara Ratovitsky, Cristian-Mihail Prada, Grace Kim, Sophia Seekins, Debra Yager, Hilda H. Slunt, Rong Wang, Mary Seeger, Allan I. Levey, Samuel E. Gandy, Neal G. Copeland, Nancy A. Jenkins, Donald L. Price, Steven G. Younkin, Sangram S. Sisodia
Journal: Neuron (1996)

Mutations in the presenilin 1 (PS1) and presenilin 2 genes cosegregate with the majority of early-onset familial Alzheimer's disease (FAD) pedigrees. We now document that the Aβ1–42(43)/Aβ1–40 ratio in the conditioned media of independent N2a cell lines expressing three FAD-linked PS1 variants is uniformly elevated relative to cells expressing similar levels of wild-type PS1. Similarly, the Aβ1–42(43)/Aβ1–40 ratio is elevated in the brains of young transgenic animals coexpressing a chimeric amyloid precursor protein (APP) and an FAD-linked PS1 variant compared with brains of transgenic mice expressing APP alone or transgenic mice coexpressing wild-type human PS1 and APP. These studies provide compelling support for the view that one mechanism by which these mutant PS1 cause AD is by increasing the extracellular concentration of Aβ peptides terminating at 42(43), species that foster Aβ deposition.
IL-25 and CD4+ TH2 cells enhance type 2 innate lymphoid cell–derived IL-13 production, which promotes IgE-mediated experimental food allergy
Authors: Jee-Boong Lee, Chun-Yu Chen, Bo Liu, Luke Mugge, Pornpimon Angkasekwinai, Valeria Facchinetti, Chen Dong, Yong-Jun Liu, Marc E. Rothenberg, Simon P. Hogan, Fred D. Finkelman, Yui-Hsi Wang
Journal: Journal of Allergy and Clinical Immunology (2015)
Chronic graft-vs.-host disease of the liver: Another indication of ursodeoxycholic acid?
Authors: Serge Erlinger
Journal: Hepatology (1992)

ABSTRACT Objective: To determine the safety and efficacy of ursodeoxycholic acid treatment in patients with chronic graft–versus–host disease (GVHD) of the liver. Design: Open–label study in which each patient served as his or her own control. Setting: Private practice and a university bone marrow transplant center. Patients: Twelve patients with refractory chronic GVHD of the liver were studied after allogeneic bone marrow transplantation. Interventions: After baseline data collection, patients were given ursodeoxycholic acid (UDCA, 10 to 15 mg/kg body weight per day) for 6 weeks. After discontinuation of the drug, patients were followed for an additional 6 weeks. Doses of immunosuppressive drugs were unchanged for these 12 weeks. Measurements: Signs, symptoms, Karnofsky performance scores, hematocrit, total leukocyte count, absolute neutrophil count, platelet count, alanine aminotransferase (ALT), aspartate aminotrasferase (AST), alkaline phosphatase, gamma–glutamyltransferase (GGT), total serum bilirubin, prothrombin time.(Text missing).
The Evolution of Male–Female Sexual Dimorphism Predates the Gender-Based Divergence of the Mating Locus Gene MAT3/RB
Authors: Rintaro Hiraide, Hiroko Kawai-Toyooka, Takashi Hamaji, Ryo Matsuzaki, Kaoru Kawafune, Jun Abe, Hiroyuki Sekimoto, James Umen, Hisayoshi Nozaki
Journal: Molecular Biology and Evolution (2013)

The molecular bases for the evolution of male–female sexual dimorphism are possible to study in volvocine algae because they encompass the entire range of reproductive morphologies from isogamy to oogamy. In 1978, Charlesworth suggested the model of a gamete size gene becoming linked to the sex-determining or mating type locus (MT) as a mechanism for the evolution of anisogamy. Here, we carried out the first comprehensive study of a candidate MT-linked oogamy gene, MAT3/RB, across the volvocine lineage. We found that evolution of anisogamy/oogamy predates the extremely high male–female divergence of MAT3 that characterizes the Volvox carteri lineage. These data demonstrate very little sex-linked sequence divergence of MAT3 between the two sexes in other volvocine groups, though linkage between MAT3 and the mating locus appears to be conserved. These data implicate genetic determinants other than or in addition to MAT3 in the evolution of anisogamy in volvocine algae.
Transfer of experimental allergic encephalomyelitis to bone marrow chimeras. Endothelial cells are not a restricting element.
Authors: D J Hinrichs, K W Wegmann, G N Dietsch
Journal: The Journal of Experimental Medicine (1987)

The adoptive transfer of clinical and histopathologic signs of experimental allergic encephalomyelitis (EAE) requires MHC compatibility between cell donor and cell recipient. The results of adoptive transfer studies using F1 to parent bone marrow chimeras as recipients of parental-derived BP-sensitive spleen cells indicate that this restriction is not expressed at the level of the endothelial cell but is confined to the cells of bone marrow derivation. Furthermore, these results indicate that the development of EAE is not dependent on the activity of MHC-restricted cytotoxic cells.
STUDIES ON THE SOLUBLE PRECIPITABLE SUBSTANCES OF VACCINIA
Authors: James Craigie, F. O. Wishart
Journal: The Journal of Experimental Medicine (1936)

1. Thermolabile and thermostable soluble precipitable substances dissociate in vitro from the elementary bodies of vaccinia. 2. These substances are serologically related to the soluble precipitable substances found in suspensions of fresh vaccine pulp.
Antitumor Vaccination of Patients With Glioblastoma Multiforme: A Pilot Study to Assess Feasibility, Safety, and Clinical Benefit
Authors: Hans Herbert Steiner, Matteo Mario Bonsanto, Philipp Beckhove, Michael Brysch, Karsten Geletneky, Rezvan Ahmadi, Rebecca Schuele-Freyer, Paul Kremer, Golamreza Ranaie, Dejana Matejic, Harald Bauer, Marika Kiessling, Stefan Kunze, Volker Schirrmacher, Christel Herold-Mende
Journal: Journal of Clinical Oncology (2004)

Purpose Prognosis of patients with glioblastoma is poor. Therefore, in glioblastoma patients, we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe. Also, we determined the influence on progression-free survival and overall survival and on vaccination-induced antitumor reactivity. Patients and Methods In a nonrandomized study, 23 patients were vaccinated and compared with nonvaccinated controls (n = 87). Vaccine was prepared from patient's tumor cell cultures by infection of the cells with Newcastle Disease Virus, followed by gamma-irradiation, and applied up to eight times. Antitumor immune reactivity was determined in skin, blood, and relapsed tumor by delayed-type hypersensitivity skin reaction, ELISPOT assay, and immunohistochemistry, respectively. Results Establishment of tumor cell cultures was successful in approximately 90% of patients. After vaccination, we observed no severe side effects. The median progression-free survival of vaccinated patients was 40 weeks (v 26 weeks in controls; log-rank test, P = .024), and the median overall survival of vaccinated patients was 100 weeks (v 49 weeks in controls; log-rank test, P &lt; .001). Forty-five percent of the controls survived 1 year, 11% survived 2 years, and there were no long-term survivors (≥ 3 years). Ninety-one percent of vaccinated patients survived 1 year, 39% survived 2 years, and 4% were long-term survivors. In the vaccinated group, immune monitoring revealed significant increases of delayed-type hypersensitivity reactivity, numbers of tumor-reactive memory T cells, and numbers of CD8 + tumor-infiltrating T-lymphocytes in secondary tumors. Conclusion Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and to improve the prognosis of patients with glioblastomas. This could be substantiated by the observed antitumor immune response.
Alveolar atypical hyperplasia in association with primary pulmonary adenocarcinoma: a clinicopathological study of 10 cases.
Authors: F A Carey, W A Wallace, R J Fergusson, K M Kerr, D Lamb
Journal: Thorax (1992)

BACKGROUND: A distinctive cytologically atypical lesion has been found in patients with primary adenocarcinoma of the lung. The aim of this study was to characterise the lesion and assess its role in tumour pathogenesis. METHODS: Lung parenchyma from 175 consecutive resection specimens for primary pulmonary adenocarcinoma were examined. Foci of atypical hyperplasia were identified. Cell proliferation state and expression of S100 and carcinoembryonic antigens were evaluated by immunohistochemistry. Clinical data on cigarette smoking and occupational exposure to carcinogens were abstracted from inpatient case notes. RESULTS: Ten cases (5.7%) with these distinctive cytologically atypical lesions were identified. The lesions showed immunohistochemical evidence of increased cell proliferation and focal carcinoembryonic antigen expression. The associated adenocarcinomas were of peripheral (parenchymal) type. There was an association with cigarette smoking and two of the 10 patients had synchronous carcinomas elsewhere in the lung. CONCLUSION: The clinical and pathological associations of these lesions suggest that they may be important in the histogenesis of primary pulmonary adenocarcinoma.
Single nucleotide polymorphisms in matrix metalloproteinase genes and lung cancer chemotherapy response and prognosis
Authors: D. B. Scherf, H. Dally, P. Müller, G. Werle-Schneider, B. Jäger, L. Edler, S. Tuengerthal, J. R. Fischer, P. Drings, H. Bartsch, A. Risch
Journal: European Respiratory Journal (2009)

The prognosis for lung cancer patients treated with chemotherapy is poor. Single nucleotide polymorphisms (SNPs) in matrix metalloproteinase (MMP) genes could influence treatment outcome by altering apoptotic pathways. Eight SNPs with known or suspected phenotypic effect in six genes ( MMP1 , MMP2, MMP3, MMP7, MMP9 and MMP12 ) were investigated. For 349 Caucasian patients with primary lung cancer, receiving first-line chemotherapy, three different endpoints were analysed: response after the second cycle, progression free survival (PFS) and overall survival (OS). The prognostic value of the SNPs was analysed using multiple logistic regression for all patients and histology-, stage- and treatment-specific subgroups. Hazard ratio estimates for PFS and OS were calculated using Cox regression methods. None of the investigated polymorphisms modified response significantly in the whole patient population. However, tumour stage IIIB variant allele carriers of MMP2 C-735T showed a significantly worse response. PFS was significantly prolonged in MMP1 G-1607GG variant allele carriers and OS in small cell lung cancer patients carrying the MMP12 A-82G variant allele. In conclusion, this study identified SNPs in MMP1 , MMP2, MMP7 and MMP12 for further investigation as possible predictors of chemotherapy outcome in lung cancer patients.