tbuckley/cabot-search huggingface dataset:
Hepatocyte-matrix interactions.
Authors: J P Iredale, M J Arthur
Journal: Gut (1994)

Hepatocyte-matrix interactionsThe normal hepatic sinusoid consists of a fenestrated endothelial capillary, behind which, and adjacent to the border of the hepatic pallisade, is the space of Disse.This term is in some respects a misnomer, for within it are the hepatic lipocytes (fat storing or Ito cells) and a specialised basement membrane-like matrix, which consists predomi- nantly of type IV collagen, laminin, and proteoglycans.Extracellular matrix is an integral part of multicellular organisms, providing structural integrity and support to cells.Current evidence indicates that matrix is not merely a simple scaffolding but a dynamic modulator of cell pheno- type and behaviour.There is now evidence that the basement membrane-like matrix of the liver can change the phenotypic characteristics and growth of lipocytes, endothelial cells, and hepatocytes.4Recent developments in matrix biochemistry and cell biology have offered a fascinating insight into the complex interaction of hepatocytes and their surrounding matrix in both health and disease.The importance of extracellular matrix was first appreciated in hepatocyte culture studies.
Interferon-lambda serum levels in hepatitis C
Authors: Bettina Langhans, Bernd Kupfer, Ingrid Braunschweiger, Simone Arndt, Wibke Schulte, Hans Dieter Nischalke, Jacob Nattermann, Johannes Oldenburg, Tilman Sauerbruch, Ulrich Spengler
Journal: Journal of Hepatology (2010)
Pharmacogenetic Study of Statin Therapy and Cholesterol Reduction
Authors: Daniel I. Chasman
Journal: JAMA (2004)

Polymorphisms in genes involved in cholesterol synthesis, absorption, and transport may affect statin efficacy.To evaluate systematically whether genetic variation influences response to pravastatin therapy.The DNA of 1536 individuals treated with pravastatin, 40 mg/d, was analyzed for 148 single-nucleotide polymorphisms (SNPs) within 10 candidate genes related to lipid metabolism. Variation within these genes was then examined for associations with changes in lipid levels observed with pravastatin therapy during a 24-week period.Changes in lipid levels in response to pravastatin therapy.Two common and tightly linked SNPs (linkage disequilibrium r2 = 0.90; heterozygote prevalence = 6.7% for both) were significantly associated with reduced efficacy of pravastatin therapy. Both of these SNPs were in the gene coding for 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the target enzyme that is inhibited by pravastatin. For example, compared with individuals homozygous for the major allele of one of the SNPs, individuals with a single copy of the minor allele had a 22% smaller reduction in total cholesterol (-32.8 vs -42.0 mg/dL [-0.85 vs -1.09 mmol/L]; P =.001; absolute difference, 9.2 mg/dL [95% confidence interval [CI], 3.8-14.6 mg/dL]) and a 19% smaller reduction in low-density lipoprotein (LDL) cholesterol (-27.7 vs -34.1 mg/dL [-0.72 vs -0.88 mmol/L]; P =.005; absolute difference, 6.4 mg/dL [95% CI, 2.2-10.6 mg/dL]). The association for total cholesterol reduction persisted even after adjusting for multiple tests on all 33 SNPs evaluated in the HMG-CoA reductase gene as well as for all 148 SNPs evaluated was similar in magnitude and direction among men and women and was present in the ethnically diverse total cohort as well as in the majority subgroup of white participants. No association for either SNP was observed for the change in high-density lipoprotein (HDL) cholesterol (P>.80) and neither was associated with baseline lipid levels among those actively treated or among those who did not receive the drug. Among the remaining genes, less robust associations were found for squalene synthase and change in total cholesterol, apolipoprotein E and change in LDL cholesterol, and cholesteryl ester transfer protein and change in HDL cholesterol, although none of these met our conservative criteria for purely pharmacogenetic effects.Individuals heterozygous for a genetic variant in the HMG-CoA reductase gene may experience significantly smaller reductions in cholesterol when treated with pravastatin.
Phase II trial of capecitabine and oxaliplatin (CAPOX) plus cetuximab in patients with metastatic colorectal cancer who progressed after oxaliplatin-based chemotherapy
Authors: J. Souglakos, A. Kalykaki, L. Vamvakas, N. Androulakis, K. Kalbakis, S. Agelaki, N. Vardakis, M. Tzardi, A.P. Kotsakis, J. Gioulbasanis, D. Tsetis, G. Sfakiotaki, D. Chatzidaki, D. Mavroudis, V. Georgoulias
Journal: Annals of Oncology (2006)
Lung function and airway responsiveness in children and adolescents after hyaline membrane disease: a matched cohort study
Authors: A Cano, F Payo
Journal: European Respiratory Journal (1997)

Some investigators consider prematurity to be responsible for the lung function abnormalities found in prematurely born children and adolescents who had neonatal respiratory diseases. This study attempts to measure the effect of neonatal respiratory disease on lung function during school age and adolescence, by controlling the confounding effect due to prematurity. Lung volumes, airway resistance and specific airway conductance measured by plethysmography, maximum expiratory flow-volume curves, pulmonary diffusion of carbon monoxide, and the airway responsiveness to a challenge with methacholine, were determined in a cohort of children aged 8-14 yrs, who had suffered from hyaline membrane disease but who did not develop bronchopulmonary dysplasia. The values obtained were compared with those of children without hyaline membrane disease, not ventilated for other causes, and matched for gestational age, sex and age. Thirty six pairs of children were enrolled, of which 26 participated in the methacholine test. Compared to their paired controls, children with hyaline membrane disease had a significantly lower forced expiratory volume in one second (FEV1), forced mid-expiratory flow (FEF25-75), and maximal expiratory flow when 75, 50 and 25% of the forced vital capacity remained in the lung (MEF75, MEF50 and MEF25, respectively), and a significantly higher airway resistance (Raw). The effect was less in children born more prematurely, who showed less difference in FEF25-75, MEF75 and MEF25. The duration of treatment with steroids in the neonatal period was associated with a reduction in the differences in FEV1, MEF25 and Raw. Independent of prematurity, hyaline membrane disease and its treatment is associated with alterations in long-term lung function, even in children who do not develop bronchopulmonary dysplasia. The effect can be less in more premature children, and neonatal steroids can have a long-term preventive effect.
Spatiotemporal regulation of intracellular trafficking of Toll-like receptor 9 by an inhibitory receptor, Ly49Q
Authors: Mariko Yoshizaki, Aya Tazawa, Eiji Kasumi, Shigemi Sasawatari, Kenji Itoh, Taeko Dohi, Takehiko Sasazuki, Kayo Inaba, Andrew P. Makrigiannis, Noriko Toyama-Sorimachi
Journal: Blood (2009)
Evolution of Viral Proteins Originated De Novo by Overprinting
Authors: Niv Sabath, Andreas Wagner, David Karlin
Journal: Molecular Biology and Evolution (2012)

New protein-coding genes can originate either through modification of existing genes or de novo. Recently, the importance of de novo origination has been recognized in eukaryotes, although eukaryotic genes originated de novo are relatively rare and difficult to identify. In contrast, viruses contain many de novo genes, namely those in which an existing gene has been "overprinted" by a new open reading frame, a process that generates a new protein-coding gene overlapping the ancestral gene. We analyzed the evolution of 12 experimentally validated viral genes that originated de novo and estimated their relative ages. We found that young de novo genes have a different codon usage from the rest of the genome. They evolve rapidly and are under positive or weak purifying selection. Thus, young de novo genes might have strain-specific functions, or no function, and would be difficult to detect using current genome annotation methods that rely on the sequence signature of purifying selection. In contrast to young de novo genes, older de novo genes have a codon usage that is similar to the rest of the genome. They evolve slowly and are under stronger purifying selection. Some of the oldest de novo genes evolve under stronger selection pressure than the ancestral gene they overlap, suggesting an evolutionary tug of war between the ancestral and the de novo gene.
FURTHER OBSERVATIONS ON THE SURVIVAL OF VACCINE VIRUS SEPARATED FROM LIVING HOST CELLS BY COLLODION MEMBRANES
Authors: Ralph S. Muckenfuss
Journal: The Journal of Experimental Medicine (1931)

The survival of vaccine virus when incubated on the opposite side of a collodion membrane from a suspension of fresh minced rabbit kidney was not complete in these experiments, and passage in series was not successful. The degree of survival seemed somewhat greater if dead cells, killed by repeated freezing and thawing, were added to the virus during incubation, although the tissue was able to increase the intensity of the skin reactions. Extracts of dead kidney cells did not increase the degree of survival, as determined by the intensity of the skin reaction. No significant or constant increase in the intensity of the skin reactions resulted from the addition of cysteine hydrochloride to the virus in the dialyzing apparatus.
Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis
Authors: Per Soelberg Sorensen, Christian Ross, Katja Maria Clemmesen, Klaus Bendtzen, Jette Lautrup Frederiksen, Kai Jensen, Ole Kristensen, Thor Petersen, Soren Rasmussen, Mads Ravnborg, Egon Stenager, Nils Koch-Henriksen
Journal: The Lancet (2003)
Changing views of the role of matrix metalloproteinases in metastasis
Authors: A. F. Chambers, L. M. Matrisian
Journal: JNCI Journal of the National Cancer Institute (1997)

Metastatic spread of cancer continues to be the greatest barrier to cancer cure. Understanding the molecular mechanisms of metastasis is crucial for the design and effective use of novel therapeutic strategies to combat metastases. One class of molecules that has been repeatedly implicated in metastasis is the matrix metalloproteinases (MMPs). In this review, we re-examine the evidence that MMPs are associated with metastasis and that they make a functional contribution to the process. Initially, it was believed that the major role of MMPs in metastasis was to facilitate the breakdown of physical barriers to metastasis, thus promoting invasion and entry into and out of blood or lymphatic vessels (intravasation, extravasation). However, recent evidence suggests that MMPs may have a more complex role in metastasis and that they may make important contributions at other steps in the metastatic process. Studies using intravital videomicroscopy, as well as experiments in which levels of MMPs or their inhibitors (tissue inhibitors of metalloproteinases [TIMPs]) are manipulated genetically or pharmacologically, suggest that MMPs are key regulators of growth of tumors, at both primary and metastatic sites. On the basis of this evidence, a new view of the functional role of MMPs in metastasis is presented, which suggests that MMPs are important in creating and maintaining an environment that supports the initiation and maintenance of growth of primary and metastatic tumors. Further clarification of the mechanisms by which MMPs regulate growth of primary and metastatic tumors will be important in the development of novel therapeutic strategies against metastases.
INPP4B Is a PtdIns(3,4,5)P3 Phosphatase That Can Act as a Tumor Suppressor
Authors: Satoshi Kofuji, Hirotaka Kimura, Hiroki Nakanishi, Hiroshi Nanjo, Shunsuke Takasuga, Hui Liu, Satoshi Eguchi, Ryotaro Nakamura, Reietsu Itoh, Noriko Ueno, Ken Asanuma, Mingguo Huang, Atsushi Koizumi, Tomonori Habuchi, Masakazu Yamazaki, Akira Suzuki, Junko Sasaki, Takehiko Sasaki
Journal: Cancer Discovery (2015)

Abstract Inositol polyphosphate 4-phosphatase B (INPP4B) has been identified as a tumor suppressor mutated in human breast, ovary, and prostate cancers. The molecular mechanism underlying INPP4B's tumor-suppressive role is currently unknown. Here, we demonstrate that INPP4B restrains tumor development by dephosphorylating the PtdIns(3,4,5)P3 that accumulates in situations of PTEN deficiency. In vitro, INPP4B directly dephosphorylates PtdIns(3,4,5)P3. In vivo, neither inactivation of Inpp4b (Inpp4bΔ/Δ) nor heterozygous deletion of Pten (Pten+/−) in mice causes thyroid abnormalities, but a combination of these mutations induces malignant thyroid cancers with lung metastases. At the molecular level, simultaneous deletion of Inpp4b and Pten synergistically increases PtdIns(3,4,5)P3 levels and activates AKT downstream signaling proteins in thyroid cells. We propose that the PtdIns(3,4,5)P3 phosphatase activity of INPP4B can function as a “back-up” mechanism when PTEN is deficient, making INPP4B a potential novel therapeutic target for PTEN-deficient or PIK3CA-activated cancers. Significance: Although INPP4B expression is reduced in several types of human cancers, our work on Inpp4B-deficient mice provides the first evidence that INPP4B is a bona fide tumor suppressor whose function is particularly important in situations of PTEN deficiency. Our biochemical data demonstrate that INPP4B directly dephosphorylates PtdIns(3,4,5)P3. Cancer Discov; 5(7); 730–9. ©2015 AACR. See related commentary by Vo and Fruman, p. 697. See related article by Chew et al., p. 740. This article is highlighted in the In This Issue feature, p. 681
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes
Authors: Gabi Kastenmüller, Maria Elisabeth Schenk, Johann Gasteiger, Hans-Werner Mewes
Journal: Genome biology (2009)

Abstract Identifying the biochemical basis of microbial phenotypes is a main objective of comparative genomics. Here we present a novel method using multivariate machine learning techniques for comparing automatically derived metabolic reconstructions of sequenced genomes on a large scale. Applying our method to 266 genomes directly led to testable hypotheses such as the link between the potential of microorganisms to cause periodontal disease and their ability to degrade histidine, a link also supported by clinical studies.
Ponatinib in Refractory Philadelphia Chromosome–Positive Leukemias
Authors: Jorge E. Cortes, Hagop Kantarjian, Neil P. Shah, Dale Bixby, Michael J. Mauro, Ian Flinn, Thomas O'Hare, Simin Hu, Narayana I. Narasimhan, Victor M. Rivera, Tim Clackson, Christopher D. Turner, Frank G. Haluska, Brian J. Druker, Michael W.N. Deininger, Moshe Talpaz
Journal: New England Journal of Medicine (2012)

Resistance to tyrosine kinase inhibitors in patients with chronic myeloid leukemia (CML) and Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph-positive ALL) is frequently caused by mutations in the BCR-ABL kinase domain. Ponatinib (AP24534) is a potent oral tyrosine kinase inhibitor that blocks native and mutated BCR-ABL, including the gatekeeper mutant T315I, which is uniformly resistant to tyrosine kinase inhibitors.
CHRONIC HYPERPLASTTC CANDIDIASIS—CANDIDAL LEUKOPLAKIA
Authors: R. A. CAWSON, T. LEHNER
Journal: British Journal of Dermatology (1968)

SUMMARY. Twelve cases of chronic hyperplastic candidiasis of the oral mucosa are described. Clinically the lesions could not be reliably differentiated from "leukoplakia" due to other causes. All but 2 of the patients were otherwise healthy. The histological appearances were distinctive: there was invasion by hyphae of C. albicans of the superficial epithelium of an acanthotic and parakeratotic plaque, associated with a characteristic intraepithelial inflammatory reaction. In 9 cases the antibody titres to C. albicans in serum and saliva supported a diagnosis of candidiasis. The response of the lesions to oral Nystatin was good in 3 cases and incomplete in 4. The evidence that C. albicans plays an essential causative rather than a secondary role is critically discussed. Recognition of chronic hyperplastic candidiasis from other "leukoplakias" is of practical importance since this condition is potentially reversible by medical treatment.
A randomized controlled trial of R-salbutamol for topical treatment of discoid lupus erythematosus
Authors: G.B.E. Jemec, S. Ullman, M. Goodfield, A. Bygum, A.B. Olesen, J. Berth-Jones, F. Nyberg, M. Cramers, J. Faergemann, P. Andersen, A. Kuhn, T. Ruzicka
Journal: British Journal of Dermatology (2009)

In a recent open pilot trial, R-salbutamol sulphate, a well-known molecule with anti-inflammatory effects, was tested successfully on patients with therapy-resistant discoid lupus erythematosus (DLE).To compare the efficacy and safety of R-salbutamol cream 0.5% vs. placebo on DLE lesions in a multicentre, double-blinded, randomized, placebo-controlled phase II trial.Thirty-seven patients with at least one newly developed DLE lesion were randomized - 19 to the R-salbutamol cream 0.5% and 18 to placebo - and treated twice daily for 8 weeks. Efficacy was evaluated through scores of erythema, scaling/hypertrophy and induration as well as pain and itching; general improvement scored by the investigator and global improvement scored by patients' assessment were also evaluated.The mean area under the curve of improvement for scaling/hypertrophy, pain, itching and global patient assessment was significantly better for the actively treated patients as compared with placebo (scaling/hypertrophy, P = 0.0262; pain, P = 0.0238; itching, P = 0.0135; global patient assessment, P = 0.045). Moreover, the percentage of patients without induration was significantly higher in the active group compared with the placebo group (P = 0.013), and a statistically significantly greater decrease in the size of the lesional area was also seen in the overall analysis of the R-salbutamol-treated patients (P = 0.0197). No serious adverse events were reported.Application of R-salbutamol cream 0.5% was safe and well tolerated. Statistically significant effects were seen on scaling/hypertrophy, induration, pain and itching as well as patient global assessment, suggesting that R-salbutamol could be a promising new topical therapy alternative for DLE.
Resource Use and Survival of Patients Hospitalized with Congestive Heart Failure: Differences in Care by Specialty of the Attending Physician
Authors: Andrew D. Auerbach, Mary Beth Hamel, Roger B. Davis, Alfred F. Connors, Carol Regueiro, Norman Desbiens, Lee Goldman, Robert M. Califf, Neal V. Dawson, Neil Wenger, Humberto Vidaillet, Russell S. Phillips
Journal: Annals of Internal Medicine (2000)

Previous studies suggest that specialty care is more costly but may produce improved outcomes for patients with acute cardiac illnesses.To determine whether patients with congestive heart failure who are cared for by cardiologists experienced differences in costs, care patterns, and survival compared with patients of generalists.Prospective cohort study.5 U.S. teaching hospitals between 1989 and 1994.1298 patients hospitalized with an exacerbation of congestive heart failure.Hospital costs; average daily Therapeutic Intervention Scoring System (TISS) score; and survival censored at 30, 180, and 365 days and 31 December 1994.Compared with patients of generalists, patients of cardiologists were younger (mean age, 63.3 and 71.4 years; P < 0.001) and had lower Acute Physiology Scores at the time of admission (35.1 and 36.7; P < 0.001) but were more likely to have a history of ventricular arrhythmias (21.0% and 10.2%; P < 0.001). At 6 months, 201 (27%) patients of cardiologists and 149 (27%) patients of generalists had died. After adjustment for sociodemographic characteristics and severity of illness, patients of cardiologists incurred costs that were 42.9% (95% CI, 27.8% to 59.8%) higher and average daily TISS scores that were 2.83 points (CI, 1.96 to 3.68 points) higher than those of patients of generalists. Patients of cardiologists were more likely to undergo right-heart catheterization (adjusted odds ratio, 2.9 [CI, 1.7 to 4.9]) or cardiac catheterization (adjusted odds ratio, 3.9 [CI, 2.4 to 6.2]) and had higher odds for transfer to an intensive care unit and electrocardiographic monitoring. Adjusted survival did not differ significantly between groups at 30 days; however, there was a trend toward improved survival among patients of cardiologists at 1 year (adjusted relative hazard, 0.82 [CI, 0.65 to 1.04]) and at maximum follow-up (adjusted relative hazard, 0.80 [CI, 0.66 to 0.96]).In this observational study of patients hospitalized with congestive heart failure, cardiologist care was associated with greater costs and resource use and no difference in survival at 30 days of follow-up. Whether the trend toward better survival at longer follow-up represents differences in care or unadjusted illness severity is uncertain.
Autologous marrow transplantation for patients with chronic myelogenous leukemia (CML) in blast crisis
Authors: M. Roy Thomas, William A. Robinson, Mary Dantas, Hubert Koeppler, Carla Drebing, L. Michael Glode
Journal: American Journal of Hematology (1984)

Abstract Eleven patients with chronic myelogenous leukemia (CML) in blast crisis were treated with chemotherapy, followed by infusion of autologous bone marrow that had been collected during the chronic phase of the disease and cryopreserved at −198°C. The mean age of the nine females and two males in this study was 34 years with an average duration of the chronic phase of the disease of 5.5 years. Seven out of the 11 patients had a splenectomy prior to intensive chemotherapy. The median survival of the first four patients who received 6‐thioguanine, cytosine arabinoside, daunorubicin (TAD) chemotherapy was 2.6 weeks and no patient reachieved the chronic phase of CML. The second group of seven patients received more intensive chemotherapy (MAdHAT), which included melphalan 30 mg/m 2 days 1, 2, and 3; Adriamycin 50 mg/m 2 intravenously (iv) day 1, hydroxyurea 1500 mg/m 2 by mouth for 5–7 days, cytosine arabinoside 100 mg/m 2 continuous infusion for 5–7 days, and VM‐26 100 mg/m 2 iv on day 3. Six out of these seven patients reachieved chronic phase CML after bone marrow reinfusion. The median survival was 29.9 weeks for all patients and 33 weeks for the six patients who reachieved chronic phase CML. All patients subsequently died of recurrent blast crisis. There was no correlation between the time of bone marrow storage and the duration of subsequent chronic phase CML. These studies have shown that autologous bone marrow transplantation after high‐dose chemotherapy can result in bone marrow engraftment with reestablishment of chronic phase CML, and prolongation of survival.
Are these data real? Statistical methods for the detection of data fabrication in clinical trials
Authors: Sanaa Al-Marzouki, Stephen Evans, Tom Marshall, Ian Roberts
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To test the application of statistical methods to detect data fabrication in a clinical trial. <b>Setting</b> Data from two clinical trials: a trial of a dietary intervention for cardiovascular disease and a trial of a drug intervention for the same problem. <b>Outcome measures</b> Baseline comparisons of means and variances of cardiovascular risk factors; digit preference overall and its pattern by group. <b>Results</b> In the dietary intervention trial, variances for 16 of the 22 variables available at baseline were significally different, and 10 significant differences were seen in means for these variables. Some of these P values were extraordinarily small. Distributions of the final recorded digit were significantly different between the intervention and the control group at baseline for 14/22 variables in the dietary trial. In the drug trial, only five variables were available, and no significant differences between the groups for baseline values in means or variances or digit preference were seen. <b>Conclusions</b> Several statistical features of the data from the dietary trial are so strongly suggestive of data fabrication that no other explanation is likely.