tbuckley/cabot-search huggingface dataset:
Risk for Bladder Cancer
Authors: J. Larry Hornsby
Journal: JAMA (1985)

Informing persons that they have been exposed to a carcinogenic chemical (beta-naphthylamine) may adversely affect these persons and their families. The purpose of this study was to identify and assess the psychological impact of a bladder cancer notification and screening program on persons at risk and their families. Approximately 140 subjects were randomly selected from 850 workers exposed to beta-naphthylamine. The Family APGAR, Impact of Event Scale, and Improved Readability Form of the Minnesota Multiphasic Personality Inventory were administered within four weeks of the initial medical screening and readministered six months later. Results show no evidence of disruption to families or substantive psychopathology among these persons. While the actual acquisition of cancer is undoubtedly a psychological trauma, mere notification of risk may not be traumatic in every situation.It has been suggested that informing people that they have been exposed to a carcinogenic chemical may have an adverse psychological impact on them and their families. This study assessed the impact on 140 randomly selected subjects from a population of 850 persons enrolled in a bladder cancer screening and notification program. Administration of psychological tests within four weeks and again six months after the medical screening showed no evidence of substantial psychopathology or family disruption. The investigators caution that additional studies in similar populations and work environments must be performed before any firm conclusions can be drawn.
Codeletions at 1p and 19q predict a lower risk of pseudoprogression in oligodendrogliomas and mixed oligoastrocytomas
Authors: Andrew L. Lin, Jingxia Liu, John Evans, Eric C. Leuthardt, Keith M. Rich, Ralph G. Dacey, Joshua L. Dowling, Albert H. Kim, Gregory J. Zipfel, Robert L. Grubb, Jiayi Huang, Clifford G. Robinson, Joseph R. Simpson, Gerald P. Linette, Michael R. Chicoine, David D. Tran
Journal: Neuro-Oncology (2013)

Pseudoprogression (PsP) occurs at a higher rate in glioblastoma multiforme with a methylated MGMT promoter—a subset with increased sensitivity to chemoradiotherapy and better overall prognosis. In oligodendroglioma (OG) and oligoastrocytoma (OA), presence of 1p/19q codeletions is highly predictive of response to treatment and is often associated with the methylated MGMT promoter; hence, this study queries whether the presence of 1p/19q codeletions in OG/OA correlates with a higher rate of PsP following therapy. A retrospective analysis was performed on all OG/OA in a database of patients with brain tumors who underwent resection of their tumor since 1998. Eighty-eight cases (37 with and 51 without 1p/19q codeletions) met inclusion criteria, and their patient data were analyzed to determine whether the presence of 1p/19q codeletions was associated with PsP and survival. OG/OA (World Health Organization grades II and III) with 1p/19q codeletions had a significantly improved survival (P = .041). Multivariate analysis found that PsP occurred less frequently in OG/OA with 1p/19q codeletions compared with tumors without codeletions (odds ratio, 0.047; 95% confidence interval, 0.005–0.426; P = .0066). The rate of PsP was 19% for the entire cohort, 31% for tumors without codeletions, and 3% for tumors with codeletions. When early posttreatment contrast enhancement developed in tumors with 1p/19q codeletions, it occurred exclusively in tumors that were histologically OA and not OG. Codeletions of 1p/19q are a marker of good prognosis but are unexpectedly associated with a lower likelihood of PsP. PsP does not correlate with sensitivity to treatment and improved survival in OG/OA.
Enteroglial-derived S100B protein integrates bacteria-induced Toll-like receptor signalling in human enteric glial cells
Authors: Fabio Turco, Giovanni Sarnelli, Carla Cirillo, Ilaria Palumbo, Francesco De Giorgi, Alessandra D'Alessandro, Marcella Cammarota, Mariateresa Giuliano, Rosario Cuomo
Journal: Gut (2013)

<h3>Objective</h3> Enteric glial cells (EGC) have been suggested to participate in host–bacteria cross-talk, playing a protective role within the gut. The way EGC interact with microorganisms is still poorly understood. We aimed to evaluate whether: EGC participate in host–bacteria interaction; S100B and Toll-like receptor (TLR) signalling converge in a common pathway leading to nitric oxide (NO) production. <h3>Design</h3> Primary cultures of human EGC were exposed to pathogenic (enteroinvasive <i>Escherichia coli</i>; EIEC) and probiotic (<i>Lactobacillus paracasei</i> F19) bacteria. Cell activation was assessed by evaluating the expression of cFos and major histocompatibility complex (MHC) class II molecules. TLR expression in EGC was evaluated at both baseline and after exposure to bacteria by real-time PCR, fluorescence microscopy and western blot analysis. S100B expression and NO release from EGC, following exposure to bacteria, were measured in the presence or absence of specific TLR and S100B pathway inhibitors. <h3>Results</h3> EIEC activated EGC by inducing the expression of cFos and MHC II. EGC expressed TLR at baseline. Pathogens and probiotics differentially modulated TLR expression in EGC. Pathogens, but not probiotics, significantly induced S100B protein overexpression and NO release from EGC. Pretreatment with specific inhibitors of TLR and S100B pathways abolished bacterial-induced NO release from EGC. <h3>Conclusions</h3> Human EGC interact with bacteria and discriminate between pathogens and probiotics via a different TLR expression and NO production. In EGC, NO release is impaired in the presence of specific inhibitors of the TLR and S100B pathways, suggesting the presence of a novel common pathway involving both TLR stimulation and S100B protein upregulation.
Delta 4-3-oxosteroid 5 beta-reductase deficiency: failure of ursodeoxycholic acid treatment and response to chenodeoxycholic acid plus cholic acid.
Authors: P T Clayton, K A Mills, A W Johnson, A Barabino, M G Marazzi
Journal: Gut (1996)

BACKGROUND--In some infants with liver disease, 3-oxo-delta 4 bile acids are the major bile acids in urine, a phenomenon attributed to reduced activity of the delta 4-3-oxosteroid 5 beta-reductase required for synthesis of chenodeoxycholic acid and cholic acid. These patients form a heterogeneous group. Many have a known cause of hepatic dysfunction and plasma concentrations of chenodeoxycholic acid and cholic acid that are actually greater than those of the 3-oxo-delta 4 bile acids. It is unlikely that these patients have a primary genetic deficiency of the 5 beta-reductase enzyme. AIMS--To document the bile acid profile, clinical phenotype, and response to treatment of an infant with cholestasis, increased plasma concentrations of 3-oxo-delta 4 bile acids, low plasma concentrations of chenodeoxycholic acid and cholic acid, and no other identifiable cause of liver disease. PATIENTS--This infant was compared with normal infants and infants with cholestasis of known cause. METHODS--Analysis of bile acids by liquid secondary ionisation mass spectrometry and gas chromatography-mass spectrometry. RESULTS--The plasma bile acid profile of the patient was unique. She had chronic cholestatic liver disease associated with malabsorption of vitamins D and E and a normal gamma-glutamyltranspeptidase when the transaminases were increased. The liver disease failed to improve with ursodeoxycholic acid but responded to a combination of chenodeoxycholic acid and cholic acid. CONCLUSION--Treatment of primary 5 beta-reductase deficiency requires the use of bile acids that inhibit cholesterol 7 alpha-hydroxylase.
Blocking indolamine 2,3 dioxygenase mediated rebound immune suppression improves systemic anti-tumor effects of radio-immunotherapy
Authors: Arta M Monjazeb, Michael Kent, Steven K Grossenbacher, William Murphy
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Immunotherapy can paradoxically up-regulate immunosuppressive pathways, a phenomenon we term “rebound immunosuppression”. One such pathway is the immunosuppressive enzyme indolamine-2,3-dioxygenase (IDO). Here, we postulated that IDO blockade will improve immunotherapy
Use of Archived Specimens in Evaluation of Prognostic and Predictive Biomarkers
Authors: R. M. Simon, S. Paik, D. F. Hayes
Journal: JNCI Journal of the National Cancer Institute (2009)

The development of tumor biomarkers ready for clinical use is complex. We propose a refined system for biomarker study design, conduct, analysis, and evaluation that incorporates a hierarchal level of evidence scale for tumor marker studies, including those using archived specimens. Although fully prospective randomized clinical trials to evaluate the medical utility of a prognostic or predictive biomarker are the gold standard, such trials are costly, so we discuss more efficient indirect "prospective–retrospective" designs using archived specimens. In particular, we propose new guidelines that stipulate that 1) adequate amounts of archived tissue must be available from enough patients from a prospective trial (which for predictive factors should generally be a randomized design) for analyses to have adequate statistical power and for the patients included in the evaluation to be clearly representative of the patients in the trial; 2) the test should be analytically and preanalytically validated for use with archived tissue; 3) the plan for biomarker evaluation should be completely specified in writing before the performance of biomarker assays on archived tissue and should be focused on evaluation of a single completely defined classifier; and 4) the results from archived specimens should be validated using specimens from one or more similar, but separate, studies.
Treatment of the Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome (IPEX) by Allogeneic Bone Marrow Transplantation
Authors: Olivier Baud, Olivier Goulet, Danielle Canioni, Françoise Le Deist, Isabelle Radford, Daniel Rieu, Sophie Dupuis-Girod, Nadine Cerf-Bensussan, Marina Cavazzana-Calvo, Nicole Brousse, Alain Fischer, Christine Rivet, Christine Bodemer, Robert Wildin, Jean-Laurent Casanova
Journal: New England Journal of Medicine (2001)

The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is a recessive disorder of early childhood.1 Symptoms of the disease generally appear in infancy and include protracted diarrhea, ichthyosiform dermatitis, insulin-dependent diabetes mellitus, thyroiditis, and hemolytic anemia.2–6 Nephropathy has been reported in two familial cases of enteropathy with insulin-dependent diabetes mellitus.7 X-linked recessive inheritance accounts for the familial cases in the seven kindreds studied to date,2–9 but sporadic cases in boys have also been reported.6,10–12 The results of immunologic investigations of IPEX1 are inconsistent with any of the known X-linked immunodeficiency diseases.13 Severe infections have been observed . . .
CAPSULAR REACTIONS AND SOLUBLE ANTIGENS OF TORULA HISTOLYTICA AND OF SPOROTRICHUM SCHENCKII
Authors: James M. Neill, Carlos G. Castillo, Robert H. Smith, Charles E. Kapros
Journal: The Journal of Experimental Medicine (1949)

The present paper deals with reactions between antiserums and the capsules of Torula histolytica (Cryptococcus hominis or Torulopsis neoformans) and of Sporotrichum schenckii. The reactions, although similar in principle to the capsular swelling seen in Quellung tests of bacteria, present a special interest because the microorganisms are larger in size and more complex in structure than bacteria. That the reactions on the capsules were caused by immunologically specific antibodies was shown by the fact that the capsular reactivity of the serums was directly related to their capacities to agglutinate suspensions and to precipitate soluble antigens of Torula and of Sporotrichum, and by the fact that the capsular reactivity was removed from the serums by absorption with soluble antigens of the respective fungi. The soluble antigens included partially purified products from broth cultures of Torula and of Sporotrichum, a partially purified product from Sporotrichum-infected mice, and a purified polysaccharide from a culture of Torula grown in a synthetic medium. The purified polysaccharide was highly reactive in precipitation tests with unabsorbed serum, and its ability to absorb the Torula capsular reactivity from the serums indicates that the major antigens on the surface of encapsulated Torula cells are polysaccharides, identical with or similar to the product used in the present study.
An unusual internal pile
Authors: K. Honein, R. Slim, F. Daniel, C. Tohme, C. Yaghi, J. Boujaoude, R. Sayegh
Journal: Gut (2007)

A 60 year old female underwent total colonoscopy for recurrent painless haematochezia. She reported no past medical history of abdominal or anorectal symptoms. Physical examination was unremarkable. …
Endothelin Axis Is a Target of the Lung Metastasis Suppressor Gene <i>RhoGDI2</i>
Authors: Brian Titus, Henry F. Frierson, Mark Conaway, Keith Ching, Theresa Guise, John Chirgwin, Garret Hampton, Dan Theodorescu
Journal: Cancer Research (2005)

Half of patients treated for locally advanced bladder cancer relapse with often fatal metastatic disease to the lung. We have recently shown that reduced expression of the GDP dissociation inhibitor, RhoGDI2, is associated with decreased survival of patients with advanced bladder cancer. However, the effectors by which RhoGDI2 affects metastasis are unknown. Here we use DNA microarrays to identify genes suppressed by RhoGDI2 reconstitution in lung metastatic bladder cancer cell lines. We identify such RNAs and focus only on those that also increase with tumor stage in human bladder cancer samples to discover only clinically relevant targets of RhoGDI2. Levels of endothelin-1 (ET-1), a potent vasoconstrictor, were affected by both RhoGDI2 reconstitution and tumor stage. To test the hypothesis that the endothelin axis is important in lung metastasis, lung metastatic bladder carcinoma cells were injected in mice treated with the endothelin receptor-specific antagonist, atrasentan, thereby blocking engagement of the up-regulated ET-1 ligand with its cognate receptor. Endothelin antagonism resulted in a dramatic reduction of lung metastases, similar to the effect of reexpressing RhoGDI2 in these metastatic cells. Taken together, these experiments show a novel approach of identifying therapeutic targets downstream of metastasis suppressor genes. The data also suggest that blockade of the ET-1 axis may prevent lung metastasis, a new therapeutic concept that warrants clinical evaluation.
Genome-wide analysis of light-regulated alternative splicing mediated by photoreceptors in Physcomitrella patens
Authors: Hshin-Ping Wu, Yi-shin Su, Hsiu-Chen Chen, Yu-Rong Chen, Chia-Chen Wu, Wen-Dar Lin, Shih-Long Tu
Journal: Genome biology (2013)

Light is one of the most important factors regulating plant growth and development. Light-sensing photoreceptors tightly regulate gene expression to control photomorphogenic responses. Although many levels of gene expression are modulated by photoreceptors, regulation at the mRNA splicing step remains unclear.We performed high-throughput mRNA sequencing to analyze light-responsive changes in alternative splicing in the moss Physcomitrella patens, and found that a large number of alternative splicing events were induced by light in the moss protonema. Light-responsive intron retention preferentially occurred in transcripts involved in photosynthesis and translation. Many of the alternatively spliced transcripts were expressed from genes with a function relating to splicing or light signaling, suggesting a potential impact on pre-mRNA splicing and photomorphogenic gene regulation in response to light. Moreover, most light-regulated intron retention was induced immediately upon light exposure, while motif analysis identified a repetitive GAA motif that may function as an exonic regulatory cis element in light-mediated alternative splicing. Further analysis in gene-disrupted mutants was consistent with a function for multiple red-light photoreceptors in the upstream regulation of light-responsive alternative splicing.Our results indicate that intensive alternative splicing occurs in non-vascular plants and that, during photomorphogenesis, light regulates alternative splicing with transcript selectivity. We further suggest that alternative splicing is rapidly fine-tuned by light to modulate gene expression and reorganize metabolic processes, and that pre-mRNA cis elements are involved in photoreceptor-mediated splicing regulation.
Multicenter Study of the Incidence of and Predictive Risk Factors for Diabetic Neuropathic Foot Ulceration
Authors: Caroline A Abbott, Loretta Vileikyte, Sheila Williamson, Anne L Carrington, Andrew JM Boulton
Journal: Diabetes Care (1998)

To investigate longitudinally prognostic factors for foot ulceration in a large population of diabetic patients with established neuropathy.A double-blind multicenter study of a potential new agent for diabetic neuropathy provided the opportunity for this 1-year investigation since intervention demonstrated no efficacy in the condition. A total of 1,035 patients with NIDDM and IDDM were included. Inclusion criteria were vibration perception threshold (VPT) at the great toe > or = 25 V in at least one foot and < or = 50 V in both feet, normal peripheral circulation, and no previous foot ulceration. VPT and clinical components of the Michigan diabetic polyneuropathy (DPN) score were assessed at baseline and subsequent visits.After 1 year, the incidence of first foot ulcers for the total population was 7.2%. Neuropathy parameters were the same between the treatment and placebo groups at baseline and were unchanged at 1 year; therefore, baseline data were combined for multiple regression analysis. VPT, age, and Michigan DPN scores for muscle strength and reflexes were significant independent predictors for first foot ulceration (P < 0.01). For each 1-U increase in VPT values at baseline, the hazard of the first foot ulcer increased by 5.6%. Similarly, for each 1-U increase in muscle strength and reflex components of the Michigan DPN scores, the hazard of the first foot ulcer increased by 5.0%.Tests of VPT and Michigan DPN scores for muscle strength and reflexes are useful clinical predictors for foot ulceration in diabetic patients with established neuropathy. The rate of subsequent ulceration in the following year was alarmingly high, however, despite standardized foot care education at baseline and regular follow-up visits.
E. Coli Meningitis: K Antigen and Virulence
Authors: C M Wilfert
Journal: Annual Review of Medicine (1978)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Genetic variants in PLG, LPA, and SIGLEC 14 as well as smoking contribute to plasma plasminogen levels
Authors: Qianyi Ma, Ayse B. Ozel, Shweta Ramdas, Beth McGee, Rami Khoriaty, David Siemieniak, Hong-Dong Li, Yuanfang Guan, Lawrence C. Brody, James L. Mills, Anne M. Molloy, David Ginsburg, Jun Z. Li, Karl C. Desch
Journal: Blood (2014)
Age-related Macular Degeneration and Modification of Systemic Complement Factor H Production Through Liver Transplantation
Authors: Samir Khandhadia, Svetlana Hakobyan, Ling Z. Heng, Jane Gibson, David H. Adams, Graeme J. Alexander, Jonathan M. Gibson, Keith R. Martin, Geeta Menon, Kathryn Nash, Sobha Sivaprasad, Sarah Ennis, Angela J. Cree, B. Paul Morgan, Andrew J. Lotery
Journal: Ophthalmology (2013)
Modulation of Bone Microenvironment with Zoledronate Enhances the Therapeutic Effects of STI571 and Paclitaxel against Experimental Bone Metastasis of Human Prostate Cancer
Authors: Sun-Jin Kim, Hisanori Uehara, Sertac Yazici, Junqin He, Robert R. Langley, Paul Mathew, Dominic Fan, Isaiah J. Fidler
Journal: Cancer Research (2005)

Prostate cancer cells metastasize to the bone where their interaction with osteoclasts and osteoblasts can lead to alterations in the structure of the bone. We determined whether the systemic administration of the bisphosphonate, zoledronate, could prevent bone lysis and halt the proliferation of human prostate cancer cells injected into the tibia of nude mice. Zoledronate did not affect the in vitro proliferation of human prostate cancer PC-3MM2 cells. The in vivo administration of zoledronate produced significant bone preservation but did not inhibit the progressive growth of PC-3MM2 cells. The systemic administration of STI571 (imatinib mesylate, Gleevec), an inhibitor of phosphorylation of the platelet-derived growth factor receptor, in combination with paclitaxel, produced apoptosis of tumor cells and bone- and tumor-associated endothelial cells. The systemic administration of zoledronate with STI571 and paclitaxel produced a significant preservation of bone structure, a decrease in tumor incidence and weight, and a decrease in incidence of lymph node metastasis. This therapeutic activity was correlated with inhibition of osteoclast function, inhibition of tumor cell proliferation, and induction of apoptosis in tumor-associated endothelial cells and tumor cells. Cancer is a heterogeneous disease that requires multimodality therapy. The present data recommend the combination of a bisphosphonate agent with protein tyrosine kinase inhibitor and an anticycling drug for the treatment of prostate cancer bone metastasis.
The Transcription Factor STAT-1 Couples Macrophage Synthesis of 25-Hydroxycholesterol to the Interferon Antiviral Response
Authors: Mathieu Blanc, Wei Yuan Hsieh, Kevin A. Robertson, Kai A. Kropp, Thorsten Forster, Guanghou Shui, Paul Lacaze, Steven Watterson, Samantha J. Griffiths, Nathanael J. Spann, Anna Meljon, Simon Talbot, Kathiresan Krishnan, Douglas F. Covey, Markus R. Wenk, Marie Craigon, Zsolts Ruzsics, Jürgen Haas, Ana Angulo, William J. Griffiths, Christopher K. Glass, Yuqin Wang, Peter Ghazal
Journal: Immunity (2012)