tbuckley/cabot-search huggingface dataset:
Regulation of Cyclooxygenase-2 Expression by the Translational Silencer TIA-1
Authors: Dan A. Dixon, Glen C. Balch, Nancy Kedersha, Paul Anderson, Guy A. Zimmerman, R. Daniel Beauchamp, Stephen M. Prescott
Journal: The Journal of Experimental Medicine (2003)

The cyclooxygenase-2 (COX-2) enzyme catalyzes the rate-limiting step of prostaglandin formation in inflammatory states, and COX-2 overexpression plays a key role in carcinogenesis. To understand the mechanisms regulating COX-2 expression, we examined its posttranscriptional regulation mediated through the AU-rich element (ARE) within the COX-2 mRNA 3′-untranslated region (3′UTR). RNA binding studies, performed to identify ARE-binding regulatory factors, demonstrated binding of the translational repressor protein TIA-1 to COX-2 mRNA. The significance of TIA-1-mediated regulation of COX-2 expression was observed in TIA-1 null fibroblasts that produced significantly more COX-2 protein than wild-type fibroblasts. However, TIA-1 deficiency did not alter COX-2 transcription or mRNA turnover. Colon cancer cells demonstrated to overexpress COX-2 through increased polysome association with COX-2 mRNA also showed defective TIA-1 binding both in vitro and in vivo. These findings implicate that TIA-1 functions as a translational silencer of COX-2 expression and support the hypothesis that dysregulated RNA-binding of TIA-1 promotes COX-2 expression in neoplasia.
Alkali Therapy In Renal Tubular Acidosis
Authors: R. Curtis Morris, Anthony Sebastian
Journal: Journal of the American Society of Nephrology (2002)

Pines and Mudge ([1][1]) coined the term “renal tubular acidosis” (RTA) to denote a renal tubular disorder that causes acidosis by restricting the reduction of urinary pH and thereby the titration of urinary buffers and excretion of acid. In extensive earlier studies of this “specific form of
The TLX1 oncogene drives aneuploidy in T cell transformation
Authors: Kim De Keersmaecker, Pedro J Real, Giusy Della Gatta, Teresa Palomero, Maria Luisa Sulis, Valeria Tosello, Pieter Van Vlierberghe, Kelly Barnes, Mireia Castillo, Xavier Sole, Michael Hadler, Jack Lenz, Peter D Aplan, Michelle Kelliher, Barbara L Kee, Pier Paolo Pandolfi, Dietmar Kappes, Fotini Gounari, Howard Petrie, Joni Van der Meulen, Frank Speleman, Elisabeth Paietta, Janis Racevskis, Peter H Wiernik, Jacob M Rowe, Jean Soulier, David Avran, Hélène Cavé, Nicole Dastugue, Susana Raimondi, Jules P P Meijerink, Carlos Cordon-Cardo, Andrea Califano, Adolfo A Ferrando
Journal: Nature Medicine (2010)
Diagnosis of house dust mite allergy
Authors: J. H. Heinig, H. Mosbech, L. Haugaard
Journal: Allergy (1991)

The medical history may be conclusively descriptive in house dust mite allergy in patients with asthma and rhinoconjunctivitis. Often the patients have both diseases. Sensibilization to D. pteronyssinus and D. farinae can be demonstrated by skin prick testing. If the diagnosis is still doubtful, the next step will be to perform a RAST test or a histamine release test. It is also important to investigate for mite exposure at the patient's residence, if the patient is suspected to be mite-allergic. Allergen challenge test in the shock organ should be performed, if hyposensitization is considered, or if, in a few cases, the mite diagnosis is still doubtful.
Phase II Randomized Trial of Autologous Formalin-Fixed Tumor Vaccine for Postsurgical Recurrence of Hepatocellular Carcinoma
Authors: Ming Kuang, Bao G. Peng, Ming D. Lu, Li J. Liang, Jie F. Huang, Qiang He, Yun P. Hua, Saeri Totsuka, Shu Q. Liu, Kam W. Leong, Tadao Ohno
Journal: Clinical Cancer Research (2004)

We conducted a Phase II clinical trial with randomized patients to determine whether autologous formalin-fixed tumor vaccine (AFTV) protects against postsurgical recurrence of hepatocellular carcinoma (HCC).Forty-one patients with HCC who had undergone curative resection were randomly allocated to the vaccine treatment (n = 19) or no adjuvant control group (n = 22). Three intradermal vaccinations were administered at 2-week intervals beginning 4-6 weeks after hepatic resection. A delayed-type hypersensitivity test was performed before and after vaccination. Primary and secondary end points are recurrence-free survival and overall survival, respectively. Observation continued until the majority of surviving patients had lived >12 months after the curative resection.In a median follow-up of 15 months, the risk of recurrence in vaccinated patients was reduced by 81% (95% confidence interval, 33-95%; P = 0.003). Vaccination significantly prolonged the time to first recurrence (P = 0.003) and improved recurrence-free survival (P = 0.003) and overall survival rates (P = 0.01). AFTV played a significant role in preventing recurrence in patients with small tumors. Adverse effects were limited to grade 1 or 2 skin toxicities such as erythema, dry desquamation, and pruritus.AFTV therapy is a safe, feasible, and effective treatment for preventing postoperational recurrence of HCC. Patients with low tumor burdens benefit from the treatment. This treatment should be advanced to a large-scale randomized trial.
Angiogenesis blockade as a new therapeutic approach to experimental colitis
Authors: S. Danese, M. Sans, D. M Spencer, I. Beck, F. Donate, M. L Plunkett, C. de la Motte, R. Redline, D. E Shaw, A. D Levine, A. P Mazar, C. Fiocchi
Journal: Gut (2006)

Neoangiogenesis is a critical component of chronic inflammatory disorders. Inhibition of angiogenesis is an effective treatment in animal models of inflammation, but has not been tested in experimental colitis.To investigate the effect of ATN-161, an anti-angiogenic compound, on the course of experimental murine colitis.Interleukin 10-deficient (IL10(-/-)) mice and wild-type mice were kept in ultra-barrier facilities (UBF) or conventional housing, and used for experimental conditions. Dextran sodium sulphate (DSS)-treated mice were used as a model of acute colitis. Mice were treated with ATN-161 or its scrambled peptide ATN-163. Mucosal neoangiogenesis and mean vascular density (MVD) were assessed by CD31 staining. A Disease Activity Index (DAI) was determined, and the severity of colitis was determined by a histological score. Colonic cytokine production was measured by ELISA, and lamina propria mononuclear cell proliferation by thymidine incorporation.MVD increased in parallel with disease progression in IL10(-/-) mice kept in conventional housing, but not in IL10(-/-) mice kept in UBF. Angiogenesis also occurred in DSS-treated animals. IL10(-/-) mice with established disease treated with ATN-161, but not with ATN-163, showed a significant and progressive decrease in DAI. The histological colitis score was significantly lower in ATN-161-treated mice than in scrambled peptide-treated mice. Inhibition of angiogenesis was confirmed by a significant decrease of MVD in ATN-161-treated mice than in ATN-163-treated mice. No therapeutic effects were observed in the DSS model of colitis. ATN-161 showed no direct immunomodulatory activity in vitro.Active angiogenesis occurs in the gut of IL10(-/-) and DSS-treated colitic mice and parallels disease progression. ATN-161 effectively decreases angiogenesis as well as clinical severity and histological inflammation in IL10(-/-) mice but not in the DDS model of inflammatory bowel disease (IBD). The results provide the rational basis for considering anti-angiogenic strategies in the treatment of IBD in humans.
IL13 gene polymorphism is a marker for psoriatic arthritis among psoriasis patients
Authors: L. Eder, V. Chandran, F. Pellett, R. Pollock, S. Shanmugarajah, C. F. Rosen, P. Rahman, D. D. Gladman
Journal: Annals of the Rheumatic Diseases (2011)

To study the association between smoking and IL13 gene polymorphisms with psoriatic arthritis (PsA) and psoriasis.The authors genotyped three groups of Caucasians: those with PsA, those with psoriasis without arthritis (PsC) and healthy controls for the rs20541 and rs848 IL13 single nucleotide polymorphisms (SNPs). An additional SNP, rs1800925, was genotyped only in the PsA and PsC groups. The differences in allelic distributions were compared by χ(2) test. The prevalence of smoking was compared between people with PsA and those with PsC. The combined effect of genotype and smoking was tested by comparing the frequencies of different combinations of rs1800925 genotype and smoking status in PsA and PsC.555 PsA patients, 342 PsC patients and 217 healthy controls were included in the study. Smoking was less prevalent in patients with PsA compared with PsC (47.4% vs 59.4%, p<0.0006). rs20541*G and rs848*C alleles were associated with PsA compared with controls (OR 1.64, p=0.0005, OR 1.61, p=0.0007 respectively). The association between these alleles and PsC compared with controls was only of borderline significance (OR 1.33, p=0.06, OR 1.26, p=0.11 respectively). Two major alleles, rs1800925*C (OR 1.28, p=0.045) and rs848*C (OR 1.30, p=0.047) were increased in PsA compared with PsC. The combination of non-smoking and the genotype rs1800925*CC was associated with increased susceptibility to PsA compared with PsC. Among smokers, rs1800925*CC was not associated with PsA compared with PsC.IL13 gene polymorphism is associated with increased susceptibility to PsA in psoriasis patients.
The pore-forming protein (perforin) of cytolytic T lymphocytes is immunologically related to the components of membrane attack complex of complement through cysteine-rich domains.
Authors: J D Young, C C Liu, L G Leong, Z A Cohn
Journal: The Journal of Experimental Medicine (1986)

Structural, functional and immunological similarities between the ninth component of complement (C9) and the lymphocyte pore-forming protein (PFP, perforin) have recently been described (8-10). PFP is shown here to be immunologically related to all other components of the membrane attack complex (MAC) of human complement, namely, C5b-6, C7, C8, and C9. Polyclonal antibodies raised against purified human C5b-6, C7, C8, or C9 react with other components of the MAC and with mouse lymphocyte PFP. The antigenic epitopes shared by human complement proteins and mouse lymphocyte PFP are limited to cysteine-rich domains. Only complement proteins that have been reduced and alkylated elicit the production of crossreactive antibodies when used as immunogens. The nonreduced forms of complement components or lymphocyte PFP neither react with these antibodies nor give rise to crossreactive antibodies. The homologous domains of complement proteins and lymphocyte PFP may play related functions in their attachment to lipid membranes and assembly of membrane lesions.
Clinical value of chromosome arms 19q and 11p losses in low-grade gliomas
Authors: Agustí Alentorn, Hinke F. van Thuijl, Yannick Marie, Hussa Alshehhi, Catherine Carpentier, Blandine Boisselier, Florence Laigle-Donadey, Karima Mokhtari, Ilari Scheinin, Pieter Wesseling, Bauke Ylstra, Laurent Capelle, Khê Hoang-Xuan, Marc Sanson, Jean-Yves Delattre, Jaap C. Reijneveld, Ahmed Idbaih
Journal: Neuro-Oncology (2013)

Diffuse low-grade gliomas (LGGs) form a heterogeneous subgroup of gliomas in adults. Chromosome (chr) arms 1p/19q codeletion and IDH mutation have been shown to be closely associated with oligodendroglial phenotype and better prognosis. We sought to identify relevant biomarkers in non 1p/19q codeleted LGGs. We characterized a retrospective series of 126 LGGs using genomic arrays, microsatellite analysis, IDH sequencing, MGMT promoter methylation assay, and p53 expression analysis. Our study confirms that 1p/19q codeletion, mutually exclusive with p53 overexpression, was associated with: (i) better prognosis, (ii) oligodendroglial phenotype, (iii) MGMT promoter methylation, and (iv) IDH mutation. Interestingly, 1p/19q codeleted tumors occur in older patients at diagnosis. Our study shows that non 1p/19q codeleted LGGs can be divided in 5 main genomic subgroups: (i) 11p loss, (ii) 19q loss (iii) 7 gain, (iv) 19 gain, and (v) unclassified. In non 1p/19q codeleted LGGs, we demonstrated that (i) 11p loss is associated with astrocytoma phenotype and has an independent negative prognostic value, and (ii) 19q loss diminished the favorable prognostic value of IDH mutation. Our findings were validated in an independent cohort of 98 LGGs. Novel genomic entities and biomarkers have been identified in non 1p/19q codeleted LGGs. Our findings may help to stratify non 1p/19q codeleted LGGs, facilitating future individualization of treatment. Further prospective studies are warranted to support our findings.
Translational Therapeutic Opportunities in Ductal Adenocarcinoma of the Pancreas
Authors: Manuel Hidalgo, Daniel D. Von Hoff
Journal: Clinical Cancer Research (2012)

Abstract Pancreatic ductal adenocarcinoma (PDA) remains a devastating disease with nearly equal incidence and mortality rates. Over the past few decades, a litany of randomized clinical trials has failed to improve the outcome of this disease. More recently, the combination chemotherapy regimen FOLFIRINOX has shown improvement in overall survival over the single agent gemcitabine, and nab-paclitaxel (an albumin-coated formulation of paclitaxel) in combination with gemcitabine has shown promising results in phase II studies. Despite limited impact on patient care as of yet, the molecular and biologic understanding of PDA has advanced substantially. This includes understanding the genomic complexity of the disease, the potential importance of the tumor microenvironment, the metabolic adaptation of PDA cells to obtain nutrients in a hypoxic environment, and the role of pancreatic cancer stem cells. These fundamental discoveries are starting to be translated into clinical studies. In this overview, we discuss the implications of biologic understanding of PDA in clinical research and provide insights for future development of novel approaches and agents in this disease. Clin Cancer Res; 18(16); 4249–56. ©2012 AACR.
Tracking the Toll of Kidney Disease
Authors: Anushree C. Shirali, Daniel R. Goldstein
Journal: Journal of the American Society of Nephrology (2008)

Since the discovery of the Toll-like receptors and their crucial role as modulators of innate immunity, there has been increasing appreciation of their role in human health and disease. Toll-like receptor signaling is critical in defending against invading microorganisms, but sustained receptor activation is also implicated in the pathogenesis of inflammatory diseases. Here we review the role of Toll-like receptors and their endogenous ligands in various renal diseases, particularly their activation in the inflammatory response of ischemic kidney injury, organ transplantation, and immune-mediated glomerulonephritis.
Functional and comparative analysis of globin loci in pufferfish and humans
Authors: Nynke Gillemans, Tara McMorrow, Rita Tewari, Albert W. K. Wai, Carola Burgtorf, Dubravka Drabek, Nicki Ventress, An Langeveld, Douglas Higgs, Kian Tan-Un, Frank Grosveld, Sjaak Philipsen
Journal: Blood (2003)
Novel Somatic and Germline Mutations in Cancer Candidate Genes in Glioblastoma, Melanoma, and Pancreatic Carcinoma
Authors: Asha Balakrishnan, Fonnet E. Bleeker, Simona Lamba, Monica Rodolfo, Maria Daniotti, Aldo Scarpa, Angela A. van Tilborg, Sieger Leenstra, Carlo Zanon, Alberto Bardelli
Journal: Cancer Research (2007)

Abstract A recent systematic sequence analysis of well-annotated human protein coding genes or consensus coding sequences led to the identification of 189 genes displaying somatic mutations in breast and colorectal cancers. Based on their mutation prevalence, a subset of these genes was identified as cancer candidate (CAN) genes as they could be potentially involved in cancer. We evaluated the mutational profiles of 19 CAN genes in the highly aggressive tumors: glioblastoma, melanoma, and pancreatic carcinoma. Among other changes, we found novel somatic mutations in EPHA3, MLL3, TECTA, FBXW7, and OBSCN, affecting amino acids not previously found to be mutated in human cancers. Interestingly, we also found a germline nucleotide variant of OBSCN that was previously reported as a somatic mutation. Our results identify specific genetic lesions in glioblastoma, melanoma, and pancreatic cancers and indicate that CAN genes and their mutational profiles are tumor specific. Some of the mutated genes, such as the tyrosine kinase EPHA3, are clearly amenable to pharmacologic intervention and could represent novel therapeutic targets for these incurable cancers. We also speculate that similar to other oncogenes and tumor suppressor genes, mutations affecting OBSCN could be involved in cancer predisposition. [Cancer Res 2007;67(8):3545–50]
Diarrhea From Vitamin C
Authors: C. Jay Hoyt
Journal: JAMA (1980)

<h3>To the Editor.—</h3> I was interested in the article "Runner's Trots: Gastrointestinal Disturbances in Runners" (243:1743, 1980), which discussed diarrhea in runners. There is another interesting source of a milder runner's diarrhea. Many runners have been advised that generous doses of vitamin C (1 g/day or more) will lessen musculoskeletal symptoms. Such doses of vitamin C frequently produce diarrhea, the source of which may be unrecognized for a long time.
Final results of phase II trial of doxorubicin HCl liposome injection followed by bexarotene in advanced cutaneous T-cell lymphoma
Authors: D.J. Straus, M. Duvic, S.M. Horwitz, K. Hymes, A. Goy, F.J. Hernandez-Ilizaliturri, T. Feldman, B. Wegner, P.L. Myskowski
Journal: Annals of Oncology (2013)
Cell signalling in pulmonary vascular cells: do not shoot the messenger!
Authors: P. H. Scott, A. J. Peacock
Journal: Thorax (1996)

Pulmonary hypertension is associated with pulmonary vascular remodelling, rendering the vessels unresponsive to vasodilators. An understanding of the mechanisms which cause this remodelling is required, which is likely to be linked to changes in vascular tone whether stimulated by hypoxia or other factors. One way to approach this is to try to understand the intracellular signalling pathways associated with hypoxia in pulmonary artery cells. This understanding could provide opportunities for therapeutic intervention using agents which will interfere with the signalling systems.
Cross-bridge kinetics in fatigued mouse diaphragm
Authors: C. Coirault, P Attal, F-X. Blanc, D Chemla, Y Lecarpentier
Journal: European Respiratory Journal (1999)

The aim of this study was to determine cross-bridge number and kinetics in the diaphragm during fatigue and early recovery. Experiments were conducted in isolated mouse diaphragm (n=10). The force of a single cross-bridge (pi), the number of cross-bridges (m x 10(9) x mm2), the time cycle (tc) and the rate constants for cross-bridge attachment (f1) and detachment (g2) were calculated from the equations of A.F. Huxley. Following the fatigue protocol, peak isometric tension (Po) and maximum unloaded shortening velocity fell by 40+/-1% and 17+/-2%, respectively. In fatigued diaphragm, m fell by approximately 40% and returned to baseline after 10 min. When compared to baseline, g2 fell in fatigued diaphragm and remained significantly lower during the 15-min recovery period. In contrast, fatigue did not significantly modify pi, f1, or tc. There was a strong linear relationship between Po and m (p<0.001, r=0.988). No relationship was observed between tc and g2. These results indicate that changes in tension during fatigue and recovery run parallel to changes in the number of active cross-bridges, with no change in the force generated per cross-bridge. It is conceivable that fatigue durably impairs adenosine diphosphate release from the actomyosin complex without modifying the total duration of the cross-bridge cycle.
Effect of Neck Compression on Sodium Excretion in Subjects with Congestive Heart Failure
Authors: THOMAS A. LOMBARDO, TINSLEY R. HARRISON
Journal: Circulation (1953)

Previous studies on normal subjects have shown that neck compression causes increased urinary excretion of sodium in the sitting position, but has little or no effect in the recumbent position. In the present study, patients with congestive heart failure have exhibited no increase in urinary sodium excretion after neck compression.
Maribavir prophylaxis for prevention of cytomegalovirus disease in recipients of allogeneic stem-cell transplants: a phase 3, double-blind, placebo-controlled, randomised trial
Authors: Francisco M Marty, Per Ljungman, Genovefa A Papanicolaou, Drew J Winston, Roy F Chemaly, Lynne Strasfeld, Jo-Anne H Young, Tulio Rodriguez, Johan Maertens, Michael Schmitt, Hermann Einsele, Augustin Ferrant, Jeffrey H Lipton, Stephen A Villano, Hongzi Chen, Michael Boeckh
Journal: The Lancet Infectious Diseases (2011)
Vasodilator Therapy for Primary Pulmonary Hypertension
Authors: H I Palevsky, A P Fishman
Journal: Annual Review of Medicine (1985)

Vasodilator Therapy for Primary Pulmonary Hypertension, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/med/36/1/annurev.me.36.020185.003023-1.gif
The use of positive pressure devices by physiotherapists
Authors: L. Denehy, S. Berney
Journal: European Respiratory Journal (2001)

The aim of this paper is to review the indications for use by physiotherapists, such as physiological rationale and the comparative efficacy of intermittent positive pressure breathing (IPPB) and continuous positive airway pressure (CPAP). A brief discussion of nasal intermittent positive airway pressure is also included. The use of IPPB for post operative prophylaxis has not been supported in the literature. In patients with low lung volumes resulting from neuromuscular disease or spinal injury, IPPB may be useful in the acute phase to improve tidal volume and cough effectiveness. The physiological benefits of CPAP to improve lung volumes are well documented in the literature. Physiotherapists use CPAP as an intermittent application in patients with low lung volumes following surgery. It is predominantly used as a second line intervention in the presence of refractory atelectasis and poor gas exchange. It may also be indicated in other patient groups with similar physiological problems. Nasal intermittent positive airway pressure combines the beneficial effects of intermittent positive pressure breathing and continuous positive airway pressure. There have been many studies evaluating its effectiveness. These have been supportive for patients with neuromuscular disease and sleep disordered breathing, but more research is needed in patients with acute respiratory failure.