tbuckley/cabot-search huggingface dataset:
The role of herpesvirus entry mediator as a negative regulator of T cell–mediated responses
Authors: Yang Wang, Sumit K. Subudhi, Robert A. Anders, James Lo, Yonglian Sun, Sarah Blink, Yugang Wang, Jing Wang, Xiaojuan Liu, Karin Mink, Daniel Degrandi, Klaus Pfeffer, Yang-Xin Fu
Journal: Journal of Clinical Investigation (2005)

Herpesvirus entry mediator (HVEM), a TNF receptor superfamily member, has been previously described as a T cell costimulatory receptor. Surprisingly, HVEM–/– T cells showed enhanced responses to in vitro concanavalin A (ConA) stimulation when compared with WT T cells. Consistent with these findings, HVEM–/– mice exhibited increased morbidity and mortality as compared with WT mice in a model of ConA-mediated T cell–dependent autoimmune hepatitis. HVEM–/– mice produced higher levels of multiple cytokines, which were dependent on the presence of CD4+ T cells. Furthermore, HVEM–/– mice were more susceptible to MOG peptide–induced experimental autoimmune encephalopathy, and they showed increased T cell proliferation and cytokine production in response to antigen-specific challenge. Taken together, our data revealed an unexpected regulatory role of HVEM in T cell–mediated immune responses and autoimmune diseases.
Coexpression of Cyclooxygenases (COX-1, COX-2) and Vascular Endothelial Growth Factors (VEGF-A, VEGF-C) in Esophageal Adenocarcinoma
Authors: Burkhard H.A. von Rahden, Hubert J. Stein, Franziska Pühringer, Ina Koch, Rupert Langer, Guido Piontek, J. Rüdiger Siewert, Heinz Höfler, Mario Sarbia
Journal: Cancer Research (2005)

Abstract Cyclooxygenases (COX), especially COX-2, are considered to be involved in carcinogenesis. Our study was initiated to test whether expression of COX isoforms (COX-1 and COX-2) is linked to expression of potent inducers of angiogenesis [vascular endothelial growth factor (VEGF)-A] and lymphangiogenesis (VEGF-C) in esophageal adenocarcinoma. One hundred twenty-three esophageal adenocarcinomas were investigated by means of quantitative reverse transcription-PCR for expression of COX-1, COX-2, VEGF-A, and VEGF-C. Additionally, COX-2 protein expression was determined using immunohistochemistry. Three esophageal cancer cell lines (OE-33, OSC-1, and OSC-2) were treated with COX-inhibiting substances (diclofenac, rofecoxib, and SC-560) and the effect on expression of the four genes was determined. COX-2 protein expression was found in all carcinomas under analysis. RNA expression levels of COX-1 and COX-2 varied markedly in carcinoma tissues and correlated significantly with each other (P &amp;lt; 0.001, r = 0.726). Furthermore, COX expression correlated with expression of VEGF-A (COX-1: P &amp;lt; 0.001, r = 0.753; COX-2: P &amp;lt; 0.001, r = 0.764) and VEGF-C (COX-1: P &amp;lt; 0.001, r = 0.778; COX-2: P &amp;lt; 0.001; r = 0.613). Exposure of esophageal cancer cell lines OE-33, OSC-1, and OSC-2 with three COX-inhibiting substances (diclofenac, rofecoxib, and SC-560) resulted in significantly reduced expression of VEGF-A and VEGF-C. In conclusion, our data suggest that both COX isoforms may be involved in the pathogenesis of esophageal adenocarcinoma, as they are linked to the expression of important modulators of angiogenesis (VEGF-A) and lymphangiogenesis (VEGF-C).
The Relationship Between Diabetic Retinopathy and Cognitive Impairment
Authors: Roxanne R. Crosby-Nwaobi, Sobha Sivaprasad, Stephanie Amiel, Angus Forbes
Journal: Diabetes Care (2013)

Recent studies have shown an increased risk for cognitive impairment and dementia in patients with diabetes. An association between diabetic retinopathy (DR) and retinal microvasculature disease and cognitive impairment has been reported as potential evidence for a microvascular component to the cognitive impairment. It was hypothesized that severity of DR would be associated with cognitive impairment in individuals with type 2 diabetes.Three hundred eighty patients with type 2 diabetes were recruited from a population-based eye screening program and grouped by severity of DR as follows: no/mild DR (n=252) and proliferative diabetic retinopathy (PDR) (n=128). Each participant underwent psychosocial assessment; depression screening; ophthalmic and physical examination, including blood assays; and cognitive assessment with the Addenbrooke's Cognitive Examination-Revised (ACE-R), Mini-Mental State Examination (MMSE), and the Mini-Cog. General linear modeling was used to examine severity of DR and cognitive impairment, adjusting for confounders.Severity of DR demonstrated an inverse relationship with cognitive impairment (fully adjusted R2=0.415, P<0.001). Ethnicity contributed most to the variance observed (16%) followed by education (7.3%) and retinopathy status (6.8%). The no/mild DR group had lower cognitive impairment scores on ACE-R (adjusted mean±SE 77.0±1.9) compared with the PDR group (82.5±2.2, P<0.001). The MMSE cutoff scores showed that 12% of the no/mild DR group (n=31) had positive screening results for dementia or significant cognitive impairment compared with 5% in the PDR group (n=6).Patients with minimal DR demonstrated more cognitive impairment than those with advanced DR. Therefore, the increased prevalence of cognitive impairment in diabetes may be associated with factors other than evident retinal microvascular disease.
Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth.
Authors: J H Kehrl, L M Wakefield, A B Roberts, S Jakowlew, M Alvarez-Mon, R Derynck, M B Sporn, A S Fauci
Journal: The Journal of Experimental Medicine (1986)

This study examines the potential role of transforming growth factor beta (TGF-beta) in the regulation of human T lymphocyte proliferation, and proposes that TGF-beta is an important autoregulatory lymphokine that limits T lymphocyte clonal expansion, and that TGF-beta production by T lymphocytes is important in T cell interactions with other cell types. TGF-beta was shown to inhibit IL-2-dependent T cell proliferation. The addition of picograms amounts of TGF-beta to cultures of IL-2-stimulated human T lymphocytes suppressed DNA synthesis by 60-80%. A potential mechanism of this inhibition was found. TGF-beta inhibited IL-2-induced upregulation of the IL-2 and transferrin receptors. Specific high-affinity receptors for TGF-beta were found both on resting and activated T cells. Cellular activation was shown to result in a five- to sixfold increase in the number of TGF-beta receptors on a per cell basis, without a change in the affinity of the receptor. Finally, the observations that activated T cells produce TGF-beta mRNA and that TGF-beta biologic activity is present in supernatants conditioned by activated T cells is strong evidence that T cells themselves are a source of TGF-beta. Resting T cells were found to have low to undetectable levels of TGF-beta mRNA, while PHA activation resulted in a rapid increase in TGF-beta mRNA levels (within 2 h). Both T4 and T8 lymphocytes were found to make mRNA for TGF-beta upon activation. Using both a soft agar assay and a competitive binding assay, TGF-beta biologic activity was found in supernatants conditioned by T cells; T cell activation resulted in a 10-50-fold increase in TGF-beta production. Thus, TGF-beta may be an important antigen-nonspecific regulator of human T cell proliferation, and important in T cell interaction with other cell types whose cellular functions are modulated by TGF-beta.
Role of mesenchymal cell populations in porcine serum-induced rat liver fibrosis
Authors: Ekapot Bhunchet, Kenjiro Wake
Journal: Hepatology (1992)

The role of liver mesenchymal cell populations in porcine serum-induced rat liver fibrosis were studied morphologically and immunohistochemically. Five-week-old rats were intraperitoneally injected with porcine serum twice a week and examined at various intervals between 3 and 24 wk after the initial injection. At an early phase, numbers of fibroblasts and extracellular matrix increased in the walls of central veins and in portal and capsular connective tissues. In the walls of central veins, the number of "second-layer cells" (i.e., the fibroblasts located at the second layer of the wall) increased. Connective tissue septa, accompanying some fibroblasts, extended from these interstitial tissues into the hepatic parenchyma, and their foremost edges came into direct contact with the perisinusoidal stellate cells. The sinusoids adjacent to the newly formed septa collapsed and later disappeared; this process resulted in the formation of hepatic limiting plates along the septa. At a more advanced stage, the interstitial fibroblasts and septal cells-which were derived from interstitial fibroblasts and the stellate cells-increased and became multilayered, constructing three-dimensional cell networks. These networks, together with increased collagen fibrils and elastic fibers, constitute the fibrotic dense connective tissue. In the control rat, smooth muscle cells were positive on vimentin, desmin and smooth muscle-alpha-actin staining. The stellate cells, second-layer cells, capsular and portal fibroblasts were shown to be vimentin and desmin positive and smooth muscle-alpha-actin negative. In the fibrotic liver, septal(fibroblastic) cells were vimentin and desmin positive and smooth muscle-alpha-actin negative. We conclude that not only the perisinusoidal stellate cells but also the interstitial fibroblasts, including the second-layer cells, play substantial role in the development of porcine serum-induced septal fibrosis in rat liver.
Transformation of Rat Liver Epithelial Cells by Kirsten Murine Sarcoma Virus23
Authors: J. S. Rhim, C. M. Kim, T. Okigaki, R. J. Huebner
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Transformation of Rat Liver Epithelial Cells by Kirsten Murine Sarcoma Virus Get access J. S. Rhim, J. S. Rhim Search for other works by this author on: Oxford Academic PubMed Google Scholar C. M. Kim, C. M. Kim Search for other works by this author on: Oxford Academic PubMed Google Scholar T. Okigaki, T. Okigaki Search for other works by this author on: Oxford Academic PubMed Google Scholar R. J. Huebner R. J. Huebner Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 5, November 1977, Pages 1509–1518, https://doi.org/10.1093/jnci/59.5.1509 Published: 01 November 1977 Article history Received: 23 February 1977 Accepted: 21 June 1977 Published: 01 November 1977
The effect of Pseudomonas aeruginosa on pulmonary function in patients with bronchiectasis
Authors: G. Davies, A. U. Wells, S. Doffman, S. Watanabe, R. Wilson
Journal: European Respiratory Journal (2006)

Bronchiectasis patients are susceptible to infection with Pseudomonas aeruginosa. Isolation is associated with increased severity of disease, greater airflow obstruction and poorer quality of life. It is not known whether infection by P. aeruginosa is a marker of disease severity or contributes to disease progression. Consecutive non-cystic fibrosis adult bronchiectasis outpatients (n = 163) with multiple sputum cultures and follow-up pulmonary function tests were designated, according to isolation of P. aeruginosa, as "never infected" (group 1; n = 67), "intermittently isolated" (group 2; n = 82) and "chronically infected" (group 3; n = 14). Based upon change in forced expiratory volume in one second (FEV(1)) % predicted levels at >or=2 yrs after presentation, longitudinal behaviour was characterised as "improvement" (>or=10% rise), "decline" (>or=10% fall) or "stability". Baseline pulmonary-function tests and longitudinal behaviour were examined in relation to pseudomonas status. There was no difference between the groups in age, sex, smoking habit or length of follow-up. Baseline FEV(1) levels were highest in group 1 (mean+/-sd: 77.4+/-24.3) and higher in group 2 (67.3+/-25.7) than in group 3 (55.2+/-18.5). The same significant trends were seen for baseline FEV(1)/forced vital capacity ratios and diffusing capacity of the lung for carbon monoxide levels. Subsequent longitudinal behaviour was linked to baseline FEV(1) levels, which were lowest in patients with improvement and lower in association with decline than with stability. However, longitudinal behaviour did not differ between groups 1, 2 and 3, either before or after adjustment for baseline FEV(1) levels. Infection by Pseudomonas aeruginosa occurs in bronchiectasis patients with more severe impairment of pulmonary function but does not influence rate of decline in pulmonary function either before or after adjustment for baseline disease severity. Thus, Pseudomonas aeruginosa is a marker of bronchiectasis severity but is not linked to an accelerated decline in pulmonary function.
Sex-related interactive effect of smoking and household pets on asthma incidence
Authors: Y. Chen, R. Dales, M. Tang, D. Krewski
Journal: European Respiratory Journal (2002)

The authors examined the interactive effect of smoking and pets at home on the incidence of asthma and the difference between sexes. The longitudinal data from the first two cycles of the National Population Health Survey, conducted in Canada, were used. A total of 12,636 subjects who reported no asthma at baseline were included in the analysis. The 2-yr cumulative incidence of asthma was higher in females than in males. Female sex and household pets demonstrated a significant interaction in the development of asthma. After adjustment for age, immigration and history of allergy, the odds ratio for smoking in relation to the asthma incidence was 2.50 (95% confidence interval: 1.24-5.05) for females who had pets at home and close to unity for those who had no pets. The incidence of asthma was not associated with smoking status and household pets in males. These results indicate that smoking, having pets at home and other environmental factors can partly explain asthma morbidity among female Canadians.
BM-23 * Twist1 EXPRESSION CONFIRMS THE ROLE OF AN EMT-LIKE PROCESS IN MEDULLOBLASTOMA METASTASIS
Authors: A. Nasir, R. Othman, L. Storer, D. Onion, A. Lourdasamy, A. Grabowska, B. Coyle
Journal: Neuro-Oncology (2014)

Medulloblastoma is an aggressive malignant embryonal tumour of the cerebellum that is frequently metastatic (one-third of primary and almost all recurrences) resulting in poor outcome. Epithelial-mesenchymal-transition (EMT) occurs during the early stages of metastasis where cells gain migratory and invasive abilities by altering phenotypically. By using a 3D in vitro culture system to better represent the in vivo microenvironment this study aims to investigate metastatic markers in medulloblastoma. Myc-immortalised cerebellar progenitor cells (C17.2), metastatic group 4 (MED1) and non-metastatic WNT subtype (MED6, C17.2 WNT) medulloblastoma cells were suspended in basement membrane extract to provide a 3D culture system. Expression of EMT genes was assessed by quantitative real time polymerase chain reaction on RNA extracted from 3D (on days 3, 6 and 8) and 2D monolayers. Twist1 expression was assessed in the MED1 primary tumour and a panel of 27 patient medulloblastomas by immunohistochemistry. Further markers were identified from published gene expression profiles of 62 medulloblastomas analysed according to metastatic status. 3D-culture of metastatic MED1 formed metabolically active branched interconnecting aggregates whilst MED6, C17.2WNT and non-tumourigenic C17.2 cells showed low metabolic activity and differentiation by day 3; supporting a non-metastatic phenotype. Expression of the Twist1 transcription factor doubled in MED1 cells grown in 3D compared to MED1 2D monolayers with no increase in expression observed in other cell types. The MED1 primary tumour showed focally high Twist1 positivity. Twist1 expression significantly correlated with metastasis in patient samples (p < 0.02). Twist1 was also expressed in spinal metastases in an orthotopic mouse model of MED1. Eight further markers differentially expressed in metastatic medulloblastoma have also been identified and are undergoing analysis. This data suggests that the EMT transcription factor Twist1 plays a role in an EMT-like process in metastatic medulloblastoma and supports the use of this 3D culture system to screen further metastatic markers.
Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors
Authors: Matthias Lechner, Garrett M Frampton, Tim Fenton, Andrew Feber, Gary Palmer, Amrita Jay, Nischalan Pillay, Martin Forster, Maureen T Cronin, Doron Lipson, Vincent A Miller, Timothy A Brennan, Stephen Henderson, Francis Vaz, Paul O'Flynn, Nicholas Kalavrezos, Roman Yelensky, Stephan Beck, Philip J Stephens, Chris Boshoff
Journal: Genome Medicine (2013)

Human papillomavirus positive (HPV+) head and neck squamous cell carcinoma (HNSCC) is an emerging disease, representing a distinct clinical and epidemiological entity. Understanding the genetic basis of this specific subtype of cancer could allow therapeutic targeting of affected pathways for a stratified medicine approach.Twenty HPV+ and 20 HPV- laser-capture microdissected oropharyngeal carcinomas were used for paired-end sequencing of hybrid-captured DNA, targeting 3,230 exons in 182 genes often mutated in cancer. Copy number alteration (CNA) profiling, Sequenom MassArray sequencing and immunohistochemistry were used to further validate findings.HPV+ and HPV- oropharyngeal carcinomas cluster into two distinct subgroups. TP53 mutations are detected in 100% of HPV negative cases and abrogation of the G1/S checkpoint by CDKN2A/B deletion and/or CCND1 amplification occurs in the majority of HPV- tumors.These findings strongly support a causal role for HPV, acting via p53 and RB pathway inhibition, in the pathogenesis of a subset of oropharyngeal cancers and suggest that studies of CDK inhibitors in HPV- disease may be warranted. Mutation and copy number alteration of PI3 kinase (PI3K) pathway components appears particularly prevalent in HPV+ tumors and assessment of these alterations may aid in the interpretation of current clinical trials of PI3K, AKT, and mTOR inhibitors in HNSCC.
Molecular evolution of pancreatic-type ribonucleases.
Authors: J J Beintema, W M Fitch, A Carsana
Journal: Molecular Biology and Evolution (1986)

Amino acid sequences of 39 mammalian ribonucleases have been used to construct trees by the maximum parsimony procedure. These trees are in fairly good agreement with the biological classification of the species involved. In the branching order of the six investigated eutherian mammalian orders, the edentates diverge first, followed, probably, by the primates. No definite conclusions can be drawn about the order of divergence of the perissodactyls, the rodents, and the group consisting of artiodactyls plus cetaceans. Nucleic acid sequences of part of the messenger RNAs of rat pancreatic and bovine seminal ribonuclease were compared. Both messengers have a second stop codon at position 129, which is in agreement with the addition of four residues at the C-terminus in several other ribonucleases. Turtle pancreatic ribonuclease and human angiogenin differ from each other and from the mammalian ribonucleases at 55%-70% of the amino acid positions; they share a number of structural features. Mammalian nonsecretory ribonucleases are homologous to the pancreatic ribonucleases in sequence regions where the active-site histidine residues are located.
Sensitivity of HTLV-I antibody assays for HTLV-II
Authors: StefanZ. Wiktor, ErnestJ. Pate, StanleyH. Weiss, RobertS. Gohd, Pelayo Correa, ElizabethT. Fontham, Barrie Hanchard, RobertJ. Biggar, WilliamA. Blattner
Journal: The Lancet (1991)
Obstructive uropathy after pan-proctocolectomy for ulcerative colitis.
Authors: M C Wilson, A R Berry, T J McNair, J W Thomson
Journal: Gut (1980)

We report two cases of pan-proctocolectomy for ulcerative colitis who some time postoperatively developed an obstructive uropathy with the clinical and radiological features of retroperitoneal fibrosis. The incidence of this complication appears to be around 10% and the possibility of such a diagnosis should be borne in mind in any patient who has non-specific symptoms after surgery for ulcerative colitis.
Effect of fenofibrate on amputation events in people with type 2 diabetes mellitus (FIELD study): a prespecified analysis of a randomised controlled trial
Authors: Kushwin Rajamani, Peter G Colman, Li Ping Li, James D Best, Merryn Voysey, Michael C D'Emden, Markku Laakso, John R Baker, Anthony C Keech
Journal: The Lancet (2009)
The Role of the Cerebellum in Voluntary Eye Movements
Authors: Farrel R Robinson, Albert F Fuchs
Journal: Annual Review of Neuroscience (2001)

In general the cerebellum is crucial for the control but not the initiation of movement. Voluntary eye movements are particularly useful for investigating the specific mechanisms underlying cerebellar control because they are precise and their brain-stem circuitry is already well understood. Here we describe single-unit and inactivation data showing that the posterior vermis and the caudal fastigial nucleus, to which it projects, provide a signal during horizontal saccades to make them fast, accurate, and consistent. The caudal fastigial nucleus also is necessary for the recovery of saccadic accuracy after actual or simulated neural or muscular damage causes horizontal saccades to be dysmetric. Saccade-related activity in the interpositus nucleus is related to vertical saccades. Both the caudal fastigial nucleus and the flocculus/paraflocculus are necessary for the normal smooth eye movements that pursue a small moving spot. By using eye movements, we have begun to uncover basic principles that give us insight into how the cerebellum may control movement in general.
Rigor Mortis in an Infant at Birth
Authors: J. A. Thompson
Journal: BMJ (1874)

affected, and did not become implicated afterwards, excepting by direct structural continuity with the focus of the disease.Secondly, the absence of any tendency towards suppuration, sloughing, or gangrene was remarkable.There was no loss of tissue up to the time of deathl; vesicationi had occurred on the surface of the growth, but the part was still covered with epithelium.There was venous turgescence in all the iinfiltrated tissucs, as indicated by the dark colour which they assumed; but microscopic examination did not indicate any marked vascularity, such as would have been the case if the develop- ment of new vessels had progressed paripassu with the growth of the disease.The original tissues became more and more swollen by a pro- cess of infiltration ; but the inew product did niot maniifest any tendency
Does the Presence of an Epiretinal Membrane Alter the Cleavage Plane during Internal Limiting Membrane Peeling?
Authors: Nihal Kenawy, David Wong, Theodore Stappler, Mario R. Romano, Ronald A. Das, Gillian Hebbar, Wendy Prime, Heinrich Heimann, Syed K. Gibran, Carl M. Sheridan, Yin Him Cheung, Paul S. Hiscott
Journal: Ophthalmology (2009)