tbuckley/cabot-search huggingface dataset:
Significance of galectin-3 immunohistochemistry , clinical characteristics, and liver imaging in differentiating intrahepatic cholangiocarcinoma from adenocarcinoma liver metastasis
Authors: A. Thamrongwitsawa, S. Kanngurn, P. Tanutit, U. Khow-Ean, P. Sunpaweravong
Journal: Journal of Clinical Oncology (2007)

15120 Background: Difficulties remain in distinguishing intrahepatic cholangiocarcinoma from adenocarcinoma liver metastasis , therefore specific immunohistochemistry markers are still needed. Galectin-3 is a beta-galactoside-binding protein and has been reported as a tissue marker in many neoplasms, including cholangiocarcinoma. Adding Galectin-3 to Cytokeratin immunohistochemistry may provide more definitive diagnosis to these conditions. Methods: Histological slides of intrahepatic cholangiocarcinoma and adenocarcinoma liver metastasis were reviewed independently by 2 pathologists to confirm diagnosis. Immunohistochemical staining was done with primary antibodies for Galectin-3 (NCL-GAL3), Cytokeratin-7 (CK-7) and Cytokeratin-20 (CK-20) in paraffin embedded tissues. The extent of Galectin-3 staining was categorized as 0% (none), 1–25% (weak), 26–65% (moderate), and &gt; 65% (strong) positive of tumor cells. Clinical characteristics and liver imaging of all patients were also reviewed. Results: Thirty-three patients were evaluated , 17 cholangiocarcinoma and 16 adenocarcinoma liver metastasis. Seventy-five percent of cholangiocarcinoma strongly expressed Galectin-3 whereas 56% of adenocarcinoma liver metastasis did. CK-7 expression was found in 47% of cholangiocarcinoma and CK-20 41%. In colorectal liver metastasis, 6 of 7 patients (85%) were negative for CK-7 and positive for CK-20. When correlated with patient characteristics, cholangiocarcinoma tended to occur in patients who were older than 55 years. Regarding liver imaging, multiple liver masses without intrahepatic bile duct dilatation correlated with adenocarcinoma liver metastasis. Conclusion: Adding Galectin-3 immunohistochemistry may benefit for differentiating intrahepatic cholangiocarcinoma from adenocarcinoma liver metastasis. Further study in a larger series is encouraged to better define role of this protein in cholangiocarcinoma diagnosis. No significant financial relationships to disclose.
High‐dose intravenous gammaglobulin (IVG) in neonatal immune thrombocytopenia
Authors: Carlos R. Suarez, Craig Anderson
Journal: American Journal of Hematology (1987)

Abstract Recent reports suggest that intravenous gammaglobulin (IVG) may be an effective treatment modality in patients with immune thrombocytopenia (ITP). Two newborns with isoimmune thrombocytopenia secondary to HLA‐A2 and PLA1 platelet antigen incompatibilities with their respective mothers and two newborns with thrombocytopenia secondary to maternal ITP were treated with IVG 400 mg/kg/day × 5 days. One patient was exposed to steroids in utero; only one mother was thrombocytopenic at the time of delivery. All patients were severely thrombocytopenic on day 1 of treatment with mean platelet count of 5.7 × 10 9 /L. All had petechiae and positive quaiac stools, and patients with isoimmune thrombocytopenia had CT scan evidence of intracranial bleeds. The mean platelet count after 24 hr was 26.7 × 10 9 /L and the average platelet increase was 21 × 10 9 /L and 33 × 10 9 /L at 24 and 48 hr, respectively. The two cases with isoimmune thrombocytopenia had sustained platelet increases; the two cases secondary to maternal ITP had transient platelet elevations. IVG can rapidly elevate the platelet count in these patients, especially those with severe bleeding manifestations.
Effects of ibuprofen on exercise-induced muscle soreness and indices of muscle damage.
Authors: A E Donnelly, R J Maughan, P H Whiting
Journal: British Journal of Sports Medicine (1990)

Thirty-two volunteers participated in a two-period crossover study in which ibuprofen was tested against an identical placebo for its effectiveness in reducing muscle soreness and damage after two bouts of downhill running. Subjective soreness, quadriceps isometric strength and isometric endurance time at 50 percent of maximum strength, serum activities of creatine kinase, lactate dehydrogenase and aspartate transaminase and serum levels of creatinine and urea were recorded at intervals up to 72 hours after exercise. Each downhill run produced muscle soreness, and a decline in muscle strength and 50 percent endurance time, although these parameters were unaffected by ibuprofen treatment. All serum parameters measured increased after both runs, but for the three enzymes this increase was smaller after the second run. Serum creatine kinase and urea levels were higher in the ibuprofen group after both runs. These results indicate that ibuprofen is not an appropriate treatment for delayed onset muscle soreness and damage.
Air pollution and upper respiratory symptoms in children from East Germany
Authors: E von Mutius, DL Sherrill, C Fritzsch, FD Martinez, MD Lebowitz
Journal: European Respiratory Journal (1995)

Whereas evidence of adverse effects of air pollution on lower respiratory tract illnesses in children is increasing, little is known about the effects of high and moderate levels of air pollution on the incidence of upper respiratory illnesses. 9 to 11 year old schoolchildren (n = 1,854) living in Leipzig, East Germany were studied. The presence of upper respiratory symptoms was documented by a physician. Daily mean and maximum concentrations of SO2, particulate matter (PM) and NOx, as well as temperature and humidity, were measured. Furthermore, a self-administered questionnaire was distributed to the parents to assess confounding factors. Parents of 1,500 (81%) children returned the questionnaire. When controlling for paternal education, passive smoke exposure, number of siblings, temperature and humidity, increased risks for the development of upper respiratory symptoms were found in the winter months for SO2 mean concentrations (odds ratio (OR) = 1.72; 95% confidence interval (95% CI) 1.19-2.49). NOx mean concentrations (OR = 1.53; 95% CI 1.01-2.31) and PM maximum values (OR = 1.62; 95% CI 1.08-2.45). In the summer months, only NOx mean concentrations were associated with a significantly increased risk (OR = 1.82; 95% CI 1.21-2.73). A combination of high mean levels of different pollutants resulted in the highest risk (OR = 2.10; 95% CI 1.30-3.37 in the winter, and OR = 2.16; 95% CI 1.23-3.81 in the summer). We conclude that high concentrations of SO2, and moderate levels of particulate matters and NOx are associated with an increased risk of developing upper respiratory symptoms in childhood.(ABSTRACT TRUNCATED AT 250 WORDS)
Mutations in PNKP cause microcephaly, seizures and defects in DNA repair
Authors: Jun Shen, Edward C Gilmore, Christine A Marshall, Mary Haddadin, John J Reynolds, Wafaa Eyaid, Adria Bodell, Brenda Barry, Danielle Gleason, Kathryn Allen, Vijay S Ganesh, Bernard S Chang, Arthur Grix, R Sean Hill, Meral Topcu, Keith W Caldecott, A James Barkovich, Christopher A Walsh
Journal: Nature Genetics (2010)
Adiponectin I164T mutation is associated with the metabolic syndrome and coronary artery disease
Authors: Koji Ohashi, Noriyuki Ouchi, Shinji Kihara, Tohru Funahashi, Tadashi Nakamura, Satoru Sumitsuji, Toshiharu Kawamoto, Satoru Matsumoto, Hiroyuki Nagaretani, Masahiro Kumada, Yoshihisa Okamoto, Hitoshi Nishizawa, Ken Kishida, Norikazu Maeda, Hisatoyo Hiraoka, Yoshio Iwashima, Kazuhiko Ishikawa, Mitsuru Ohishi, Tomohiro Katsuya, Hiromi Rakugi, Toshio Ogihara, Yuji Matsuzawa
Journal: Journal of the American College of Cardiology (2004)
DISTRIBUTION OF FIBROBLAST SURFACE ANTIGEN
Authors: Jorma Wartiovaara, Ewert Linder, Erkki Ruoslahti, Antti Vaheri
Journal: The Journal of Experimental Medicine (1974)

The localization of a cell type-specific, soluble fibroblast surface antigen (SFA) was studied by immunofluorescence and by scanning electron microscopy of the same cells. The antigen had an uneven distribution forming streaks on chick embryo fibroblasts. It was localized to membrane processes and ridges, with a diameter of 50–200 nm. The processes extended from the periphery of the cells to the substratum or to other cells. Trypsin treatment completely removed detectable amounts of SFA. The antigen was detectable within 1 h after trypsin-treated cells were reseeded. The reappearance of SFA correlated with the restoration of membrane processes. Fibroblasts transformed by Rous sarcoma virus (RSV) showed loss of all or most SFA. When normal cells were transformed without subcultivation and trypsinization a fibrillar extracellular network of SFA remained under the transformed fibroblasts while the cells themselves were negative in immunofluorescence. When fibroblasts infected by RSV mutants were transferred to nonpermissive temperature for transformation new SFA was detected within 2 h. These data lead us to propose that loss of stabilizing and anchoring effect of SFA molecules in fibrillar cell surface structures may be critical in altered growth control and malignant transformation.
STUDIES OF ADENOVIRUS SV40 HYBRID VIRUSES
Authors: Wallace P. Rowe, Stephen G. Baum, Wendell E. Pugh, M. David Hoggan
Journal: The Journal of Experimental Medicine (1965)

The titers of adenovirus and SV40 genetic carriers in hybrid preparations (E46(+)) can be quantitated by determining the percentage of cells showing neoantigens stainable with fluorescent antibody (FA) at 21 to 24 hours; both titers can be obtained with a single coverslip. The adenovirus and SV40 antigen-inducing titers so obtained are of the same order of magnitude in stock preparations of E46(+) grown in either African green monkey kidney (AGMK) or human embryonic kidney tissue culture (HEK), and are generally within one log of the infectivity titer. Quantitative studies of 50 degrees C heat inactivation, ultracentrifugation, and equilibrium density gradient centrifugation of E46(+) gave no indication that SV40 neoantigen induction could be dissociated from adenovirus, whereas adenovirus and SV40 virus grown as a mixed infection were readily dissociated by these procedures. Pretreatment of HEK cells with a medium containing 5-fluorouracil desoxyriboside (FUDR) did not affect induction of either adenovirus or SV40 neoantigen or development of cytopathic effects after infection with E46(+), but did prevent formation of Ad. 7 viral antigen.
Phylogenetic analysis of carbamoylphosphate synthetase genes: complex evolutionary history includes an internal duplication within a gene which can root the tree of life
Authors: F S Lawson, R L Charlebois, J A Dillon
Journal: Molecular Biology and Evolution (1996)

Carbamoylphosphate synthetase (CPS) catalyzes the first committed step in pyrimidine biosynthesis, arginine biosynthesis, or the urea cycle. Organisms may contain either one generalized or two specific CPS enzymes, and these enzymes may be heterodimeric (encoded by linked or unlinked genes), monomeric, or part of a multifunctional protein. In order to help elucidate the evolution of CPS, we have performed a comprehensive phylogenetic analysis using the 21 available complete CPS sequences, including a sequence from Sulfolobus solfataricus P2 which we report in this paper. This is the first report of a complete CPS gene sequence from an archaeon, and sequence analysis suggests that it encodes an enzyme similar to heterodimeric CPSII. We confirm that internal similarity within the synthetase domain of CPS is the result of an ancient gene duplication that preceded the divergence of the Bacteria, Archaea, and Eukarya, and use this internal duplication in phylogenetic tree construction to root the tree of life. Our analysis indicates with high confidence that this archaeal sequence is more closely related to those of Eukarya than to those of Bacteria. In addition to this ancient duplication which created the synthetase domain, our phylogenetic analysis reveals a complex history of further gene duplications, fusions, and other events which have played an integral part in the evolution of CPS.
Computational Modeling of Cardiac Valve Function and Intervention
Authors: Wei Sun, Caitlin Martin, Thuy Pham
Journal: Annual Review of Biomedical Engineering (2014)

In the past two decades, major advances have been made in the clinical evaluation and treatment of valvular heart disease owing to the advent of noninvasive cardiac imaging modalities. In clinical practice, valvular disease evaluation is typically performed on two-dimensional (2D) images, even though most imaging modalities offer three-dimensional (3D) volumetric, time-resolved data. Such 3D data offer researchers the possibility to reconstruct the 3D geometry of heart valves at a patient-specific level. When these data are integrated with computational models, native heart valve biomechanical function can be investigated, and preoperative planning tools can be developed. In this review, we outline the advances in valve geometry reconstruction, tissue property modeling, and loading and boundary definitions for the purpose of realistic computational structural analysis of cardiac valve function and intervention.
Hepatitis and liver dysfunction with rifampicin therapy for pruritus in primary biliary cirrhosis
Authors: M I Prince
Journal: Gut (2002)

There is evidence to suggest that rifampicin is an effective second line therapy for controlling pruritus in patients with chronic cholestatic liver disease. It is most widely used as an antipruritic agent in the autoimmune cholestatic liver disease, primary biliary cirrhosis (PBC). Rifampicin has been reported as causing hepatitis in patients being treated for tuberculosis. Most reports of this have been confounded however by the concurrent use of other hepatotoxic antitubercular therapy. Here we report a single centre experience of the use of rifampicin in PBC, and describe three cases of significant hepatitis associated with rifampicin therapy. Two of these patients had significant impairment of liver synthetic function (necessitating liver transplantation in one case). These are the first reports of impaired hepatic synthetic function due to rifampicin monotherapy. Rifampicin caused significant hepatitis in 7.3% (95% confidence interval 2.5–19.4%) of patients treated for cholestatic liver disease in our centre.
c-kit ligand: a unique potentiator of mediator release by human lung mast cells.
Authors: S C Bischoff, C A Dahinden
Journal: The Journal of Experimental Medicine (1992)

Mast cells (MC) play a central role in extrinsic allergic reactions such as asthma and may participate in other inflammatory and fibrotic processes. However, with the exception of immunoglobulin E (IgE) receptor-dependent stimulation, no secretagogues of human lung MC have yet been described. It is also unclear whether mediator release can be regulated by certain cytokines as demonstrated previously in basophils and other human inflammatory effector cells. Here, we show that the c-kit ligand (KL), a recently identified stem cell growth factor, at concentrations 10-100 times lower than that required to promote cell proliferation, enhances the release of histamine and leukotriene C4 in response to IgE receptor crosslinking of human lung MC. KL does not induce mediator release per se, but increases the sensitivity of MC to anti-IgE receptor stimulation and also enhances mediator release to maximally effective concentrations of anti-IgE receptor antibody. By contrast, a large number of cytokines examined, including the mast cell growth factors/agonists in rodents, interleukin 3 (IL-3), IL-4, IL-9, and nerve growth factor, were ineffective in this respect. These findings suggest a unique role of KL in regulating effector functions of human mucosal MC.
The HCMV Gene Products US11 and US2 Differ in Their Ability to Attack Allelic Forms of Murine Major Histocompatibility Complex (MHC) Class I Heavy Chains
Authors: Robert P. Machold, Emmanuel J.H.J. Wiertz, Thomas R. Jones, H.L. Ploegh
Journal: The Journal of Experimental Medicine (1997)

Human cytomegalovirus downregulates the expression of human class I major histocompatibility complex (MHC) molecules by accelerating destruction of newly synthesized class I heavy chains. The HCMV genome contains at least two genes, US11 and US2, each of which encode a product sufficient for causing the dislocation of newly synthesized class I heavy chains from the lumen of the endoplasmic reticulum to the cytosol. Based on a comparison of their abilities to degrade the murine class I molecules H-2Kb, Kd, Db, Dd, and Ld, the US11 and US2 gene products have non-identical specificities for class I molecules. Specifically, in human astrocytoma cells (U373-MG) transfected with the US11 gene, the Kb, Db, Dd, and Ld molecules expressed via recombinant vaccinia virus are rapidly degraded, whereas in US2-transfected cells, only Db and Dd are significantly destabilized. The diversity in HCMV-encoded functions that interfere with class I–restricted presentation likely evolved in response to the polymorphism of the MHC.
Vesicular Neurotransmitter Transporters as Targets for Endogenous and Exogenous Toxic Substances
Authors: Farrukh A. Chaudhry, Robert H. Edwards, Frode Fonnum
Journal: The Annual Review of Pharmacology and Toxicology (2007)

Exocytotic release of neurotransmitters requires their accumulation inside preformed secretory vesicles. Distinct vesicular transport activities translocate classical transmitters into synaptic vesicles energized by a H + electrochemical gradient (Δμ H + ), with subtle but important differences in dependence on the electrical and chemical components. The vesicular transporters also interact with toxic compounds and drugs. They mediate neuroprotection by sequestering toxic compounds as well as neurotransmitters into vesicles, reducing their concentration in the cytosol where they may have detrimental effects. Both therapeutic agents and psychostimulants interfering with vesicular transport have yielded insight into the pathogenesis of psychiatric as well as neurodegenerative diseases. Thus, specific inhibitors have helped to characterize both the physiological role and mechanism of vesicular neurotransmitter transport.
Pretreatment with an inhaled alpha 1-adrenergic agonist, methoxamine, reduces exercise-induced asthma
Authors: AT Dinh Xuan, M Chaussain, J Regnard, A Lockhart
Journal: European Respiratory Journal (1989)

In order to assess the role of the bronchial circulation in the pathogenesis of exercise-induced asthma (EIA), we conducted a double-blind, randomized study of the effects of pretreatment with an inhaled alpha 1-adrenergic agonist, methoxamine (Mx), in nine asthmatic teenagers with known EIA. Exercise consisted of 5 min cycle ergometry at a submaximal, constant work-load, while the subjects breathed dry air at ambient temperature. Forced expiratory volume in one second (FEV1) was measured at baseline, 15 min after pretreatment of either Mx or saline, and serially after exercise. Mx significantly reduced the exercise-induced fall of FEV1 without modifying baseline FEV1 in five of the eight subjects, had little or no effect in three and caused an acute asthmatic attack in the remaining subject. Mx has potent constrictor effects on both bronchial and vascular smooth muscles through stimulation of postjunctional alpha 1-adrenoceptors. Therefore, the protective effect of Mx on EIA may be attributed to vasoconstriction of tracheobronchial vessels opposing the hyperaemia and mucosal airway oedema that may cause, at least in part, the exercise-induced acute bronchial obstruction in EIA. Alternatively, Mx stimulates mucus, water and electrolyte secretion by airway epithelium and may, therefore, oppose the dehydration of airway surface that could be a causative factor of EIA.
Hsp27 Regulates Epithelial Mesenchymal Transition, Metastasis, and Circulating Tumor Cells in Prostate Cancer
Authors: Masaki Shiota, Jennifer L. Bishop, Ka Mun Nip, Anousheh Zardan, Ario Takeuchi, Thomas Cordonnier, Eliana Beraldi, Jenny Bazov, Ladan Fazli, Kim Chi, Martin Gleave, Amina Zoubeidi
Journal: Cancer Research (2013)

Defining the mechanisms underlying metastatic progression of prostate cancer may lead to insights into how to decrease morbidity and mortality in this disease. An important determinant of metastasis is epithelial-to-mesenchymal transition (EMT), and the mechanisms that control the process of EMT in cancer cells are still emerging. Here, we report that the molecular chaperone Hsp27 (HSPB1) drives EMT in prostate cancer, whereas its attenuation reverses EMT and decreases cell migration, invasion, and matrix metalloproteinase activity. Mechanistically, silencing Hsp27 decreased IL-6-dependent STAT3 phosphorylation, nuclear translocation, and STAT3 binding to the Twist promoter, suggesting that Hsp27 is required for IL-6-mediated EMT via modulation of STAT3/Twist signaling. We observed a correlation between Hsp27 and Twist in patients with prostate cancer, with Hsp27 and Twist expression each elevated in high-grade prostate cancer tumors. Hsp27 inhibition by OGX-427, an antisense therapy currently in phase II trials, reduced tumor metastasis in a murine model of prostate cancer. More importantly, OGX-427 treatment decreased the number of circulating tumor cells in patients with metastatic castration-resistant prostate cancer in a phase I clinical trial. Overall, this study defines Hsp27 as a critical regulator of IL-6-dependent and IL-6-independent EMT, validating this chaperone as a therapeutic target to treat metastatic prostate cancer.
Top down or bottom up? Competing management structures in the morphogenesis of colorectal neoplasms
Authors: N A Wright
Journal: Gut (2002)

Modifier genes may influence the severity, or adenoma number, of familial adenomatous polyposis in humans through tumour initiation rather than progression

One of the earliest tumour suppressor genes to be identified was APC. Germline mutations in APC are found in familial adenomatous polyposis (FAP) and second hits lead to the development of often many hundreds of adenomas in the colon and rectum, some of which progress to cancer if untreated. Many sporadic adenomas, and their ensuing carcinomas, show APC mutations, and FAP remains an important paradigm for the commoner sporadic form. Thus recent studies from the Tomlinson laboratory1 show a very close linear relationship between the macroscopic—or naked eye—count of adenomas in excised FAP colons and the count made microscopically from adenomas occupying one crypt (the unicryptal or monocryptal adenoma, fig 1) upwards. Such a close relationship strongly indicates that progression from microadenomas to macroscopic size is essentially random, that variation in disease severity (number of adenomas) results from differences in the number of microadenomas rather than disease progression, and importantly, that the selective advantages provided by different APC mutations act on tumour initiation rather than progression. A paper in this issue of Gut , also from the Tomlinson laboratory,2 analyses the effects of putative modifier genes: the severity of the disease was related to the site of the mutation, as might be expected, but first degree relatives showed polyp counts which were more similar than more distant relatives [see page 420] . These observations indicate that modifier genes influence the severity of FAP, again through tumour initiation. Furthermore, the finding of a constant microadenoma density as the colon is traversed1 suggests that initiation …