tbuckley/cabot-search huggingface dataset:
Paradox of gastric cardia: it becomes more acidic following meals while the rest of stomach becomes less acidic
Authors: A T Clarke, A A Wirz, J P Seenan, J J Manning, D Gillen, K E L McColl
Journal: Gut (2008)

<h3>Introduction:</h3> The proximal cardia region of the stomach has a high incidence of inflammation, metaplasia and neoplasia. It demonstrates less acid buffering following meals than the more distal stomach. Novel high definition pHmetry was employed to investigate acidity at the cardia under fasting conditions and in response to a meal. <h3>Methods:</h3> 15 healthy subjects were studied. A custom-made 12-electrode pH catheter was clipped at the squamocolumnar junction with four electrodes recording proximal to and eight distal to the squamocolumnar junction. The most distal pH electrode was located at the catheter tip, and nine electrodes in the region of the squamocolumnar junction were 11 mm apart. <h3>Results:</h3> The electrode situated in the cardia 5.5 mm distal to the squamocolumnar junction differed from all other intragastric electrodes during fasting in recording minimal acidity (pH &lt;4 = 2.2%) while all other intragastric electrodes recorded high intragastric acidity (pH &lt;4 = &gt;39%) (p&lt;0.05). The cardia also differed from the rest of the stomach, showing a marked increase in acidity in response to the meal (from 2.2% fasting to 58.4% at 60–70 min after the meal; p&lt;0.05) while the electrodes distal to the cardia all showed a marked decrease in acidity (p&lt;0.05). These changes in acidity at the cardia following the meal caused the gastric acidity to extend 10 mm closer to the squamocolumnar junction. <h3>Conclusion:</h3> Whereas the rest of the stomach shows a marked fall in acidity on ingesting a meal, the cardia paradoxically increases in acidity to become the most acidic region throughout the postprandial period.
Antibodies to the five histones and poly(adenosine diphosphate-ribose) in drug induced lupus: implications for pathogenesis.
Authors: R N Hobbs, A L Clayton, R M Bernstein
Journal: Annals of the Rheumatic Diseases (1987)

Certain drugs are a frequent source of antinuclear antibody (ANA) induction, and ANA is invariably present in the few patients who progress to the drug induced lupus syndrome. This report concerns the fine specificity of the ANA response to hydralazine, penicillamine, and sulphasalazine therapy. Using highly purified individual histones in fluorimetric assays, antihistone antibodies are always detectable, often in large amounts, but the pattern of response to individual histones is variable and not drug specific. In addition to the response to the three histones H1, H2B, and H3 reminiscent of idiopathic systemic lupus erythematosus, antibody to histone H2A predominates in some drug induced cases. Contrary to previous thought, histones are not the sole target of the antinuclear response: we also demonstrate a significant correlation between ANA titre and antibody to poly(adenosine diphosphate-ribose). Like the histones, this is a macromolecule that can bind to deoxyribonucleic acid (DNA). It is proposed that drug induced damage to chromatin leads to ANA production, while drug induced impairment of complement activity may then enable these autoantibodies to mediate the lupus syndrome.
Relation of Measures of Sleep-Disordered Breathing to Neuropsychological Functioning
Authors: NANCY ADAMS, MILTON STRAUSS, MARK SCHLUCHTER, SUSAN REDLINE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Sleep-disordered breathing (SDB) has been associated with neuropsychological (NP) deficits. The extent to which such effects are attributable to unmeasured confounders or selection biases, or are manifest across a range of SDB is unclear. The relationship of SDB with a broad range of NP functions was examined in 100 volunteers with a spectrum of SDB and without underlying comorbidity. Factor analysis suggested that the NP tests could be summarized as four constructs: declarative memory, signal discrimination, working memory, and set shifting. These factors plus vigilance were dependent variables. Independent variables were age, the respiratory disturbance index (RDI), a sleepiness score, the arousal index, and sleep-associated hypoxemia. Factors "declarative memory" (measuring 25% of the common variance, α = 0.95), "signal discrimination" (10% variance, α = 0.70), and "working memory" (9% variance, α = 0.52) were each significantly, linearly predicted by hypoxemia and/or the RDI, with no evidence for significant threshold effects. SDB measures accounted for 4–6% of the variance in NP constructs. In contrast, sleepiness best predicted vigilance. Thus, adverse exposures (hypoxemia or RDI) during sleep may negatively influence NP functions in a dose–response relationship, and, other than vigilance, these effects may not be directly attributable to sleepiness.
A CASE OF EHLERS-DANLOS SYNDROME
Authors: MASON BOLAM
Journal: British Journal of Dermatology (1938)

Journal Article A CASE OF EHLERS‐DANLOS SYNDROME Get access MASON BOLAM, M.A., M.B., B.CH. MASON BOLAM, M.A., M.B., B.CH. Hon. Assistant, Skin‐Department, Royal Victoria Infirmary, Newcastle‐upon‐Tyne Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 50, Issue 4, 1 April 1938, Pages 174–181, https://doi.org/10.1111/j.1365-2133.1938.tb10529.x Published: 01 April 1938
Pathogenesis of Obstructive and Central Sleep Apnea
Authors: David P. White
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Considerable progress has been made over the last several decades in our understanding of the pathophysiology of both central and obstructive sleep apnea. Central sleep apnea, in its various forms, is generally the product of an unstable ventilatory control system (high loop gain) with increased controller gain (high hypercapnic responsiveness) generally being the cause. High plant gain can contribute under certain circumstances (hypercapnic patients). On the other hand, obstructive sleep apnea can develop as the result of a variety of physiologic characteristics. The combinations of these may vary considerably between patients. Most obstructive apnea patients have an anatomically small upper airway with augmented pharyngeal dilator muscle activation maintaining airway patency awake, but not asleep. However, individual variability in several phenotypic characteristics may ultimately determine who develops apnea and how severe the apnea will be. These include: (1) upper airway anatomy, (2) the ability of upper airway dilator muscles to respond to rising intrapharyngeal negative pressure and increasing Co(2) during sleep, (3) arousal threshold in response to respiratory stimulation, and (4) loop gain (ventilatory control instability). As a result, patients may respond to different therapeutic approaches based on the predominant abnormality leading to the sleep-disordered breathing.
The Management of Gastrointestinal Stromal Tumors: A Model for Targeted and Multidisciplinary Therapy of Malignancy
Authors: Heikki Joensuu, Ronald P. DeMatteo
Journal: Annual Review of Medicine (2011)

Gastrointestinal stromal tumor (GIST) has become a model for targeted therapy in cancer. The vast majority of GISTs contain an activating mutation in either the KIT or platelet-derived growth factor A (PDGFRA) gene. GIST is highly responsive to several selective tyrosine kinase inhibitors. In fact, this cancer has been converted to a chronic disease in some patients. Considerable progress has been made recently in our understanding of the natural history and molecular biology of GIST, risk stratification, and drug resistance. Despite the efficacy of targeted therapy, though, surgery remains the only curative primary treatment and cures &gt;50% of GIST patients who present with localized disease. Adjuvant therapy with imatinib prolongs recurrence-free survival and may improve overall survival. Combined or sequential use of tyrosine kinase inhibitors with other agents following tumor molecular subtyping is an attractive next step in the management of GIST.
An analysis of psychotherapy versus placebo studies
Authors: Leslie Prioleau, Martha Murdock, Nathan Brody
Journal: Behavioral and Brain Sciences (1983)

Abstract Smith, Glass, and Miller (1980) have reported a meta-analysis of over 500 studies comparing some form of psychological therapy with a control condition. They report that when averaged over all dependent measures of outcome, psychological therapy is. 85 standard deviations better than the control treatment. We examined the subset of studies included in the Smith et al. metaanalysis that contained a psychotherapy and a placebo treatment. The median of the mean effect sizes for these 32 studies was. 15. There was a nonsignificant inverse relationship between mean outcome and the following: sample size, duration of therapy, use of measures of outcome other than undisguised self-report, measurement of outcome at follow-up, and use of real patients rather than subjects solicited for the purposes of participation in a research study. A qualitative analysis of the studies in terms of the type of patient involved indicates that those using psychiatric outpatients had essentially zero effect sizes and that none using psychiatric inpaticnts provide convincing evidence for psychotherapeutic effectiveness. The onty studies clearly demonstrating significant effects of psychotherapy were the ones that did not use real patients. For the most part, these studies involved small samples of subjects and brief treatments, occasionally described in quasibeliavioristic language. It was concluded that for real patients there is no evidence that the benefits of psychotherapy are greater than those of placebo treatment.
Cytochrome P450 1 Genes in Early Deuterostomes (Tunicates and Sea Urchins) and Vertebrates (Chicken and Frog): Origin and Diversification of the CYP1 Gene Family
Authors: J. V. Goldstone, H. M. H. Goldstone, A. M. Morrison, A. Tarrant, S. E. Kern, B. R. Woodin, J. J. Stegeman
Journal: Molecular Biology and Evolution (2007)

Cytochrome P450 family 1 (CYP1) proteins are important in a large number of toxicological processes. CYP1A and CYP1B genes are well known in mammals, but the evolutionary history of the CYP1 family as a whole is obscure; that history may provide insight into endogenous functions of CYP1 enzymes. Here, we identify CYP1-like genes in early deuterostomes (tunicates and echinoderms), and several new CYP1 genes in vertebrates (chicken, Gallus gallus and frog, Xenopus tropicalis). Profile hidden Markov models (HMMs) generated from vertebrate CYP1A and CYP1B protein sequences were used to identify 5 potential CYP1 homologs in the tunicate Ciona intestinalis genome. The C. intestinalis genes were cloned and sequenced, confirming the predicted sequences. Orthologs of 4 of these genes were found in the Ciona savignyi genome. Bayesian phylogenetic analyses group the tunicate genes in the CYP1 family, provisionally in 2 new subfamilies, CYP1E and CYP1F, which fall in the CYP1A and CYP1B/1C clades. Bayesian and maximum likelihood analyses predict functional divergence between the tunicate and vertebrate CYP1s, and regions within CYP substrate recognition sites were found to differ significantly in position-specific substitution rates between tunicates and vertebrates. Subsequently, 10 CYP1-like genes were found in the echinoderm Strongylocentrotus purpuratus (sea urchin) genome. Several of the tunicate and echinoderm CYP1-like genes are expressed during development. Canonical xenobiotic response elements are present in the upstream genomic sequences of most tunicate and sea urchin CYP1s, and both groups are predicted to possess an aryl hydrocarbon receptor (AHR), suggesting possible regulatory linkage of AHR and these CYPs. The CYP1 family has undergone multiple rounds of gene duplication followed by functional divergence, with at least one gene lost in mammals. This study provides new insight into the origin and evolution of CYP1 genes.
The EGFR Ligands Amphiregulin and Heparin-Binding EGF-like Growth Factor Promote Peritoneal Carcinomatosis in CXCR4-Expressing Gastric Cancer
Authors: Kazuo Yasumoto, Tadaaki Yamada, Atsuhiro Kawashima, Wei Wang, Qi Li, Ivan Shterev Donev, Shinji Tacheuchi, Hisatsugu Mouri, Kaname Yamashita, Koushiro Ohtsubo, Seiji Yano
Journal: Clinical Cancer Research (2011)

Peritoneal carcinomatosis, often associated with malignant ascites, is the most frequent cause of death in patients with advanced gastric cancer. We previously showed that the CXCR4/CXCL12 axis is involved in the development of peritoneal carcinomatosis from gastric cancer. Here, we investigated whether epidermal growth factor receptor (EGFR) ligands are also involved in the development of peritoneal carcinomatosis from gastric cancer.The functional involvement of expression of the ErbB family of receptors and/or EGFR ligands was examined in CXCR4-expressing human gastric cancer cells and fibroblasts, clinical samples (primary tumors and ascites), and an animal model.High concentration of the EGFR ligands amphiregulin and heparin-binding EGF-like growth factor (HB-EGF), as well as of CXCL12, were present in malignant ascites. Human gastric cancer cell lines and primary gastric tumors, with high potential to generate peritoneal carcinomatosis, expressed high levels of EGFR and CXCR4 mRNA and protein. Both amphiregulin and HB-EGF enhanced the proliferation, migration, and functional CXCR4 expression in highly CXCR4-expressing gastric cancer NUGC4 cells. Amphiregulin strongly enhanced the proliferation of NUGC4 cells, whereas HB-EGF markedly induced the migration of fibroblasts. Moreover, HB-EGF and CXCL12 together enhanced TNFα-converting enzyme (TACE)-dependent amphiregulin shedding from NUGC4 cells. In an experimental peritoneal carcinomatosis model in mice, cetuximab effectively reduced tumor growth and ascites formation.Our results strongly suggest that the EGFR ligands amphiregulin and HB-EGF play an important role, interacting with the CXCL12/CXCR4 axis, in the development of peritoneal carcinomatosis from gastric cancer, indicating that these two axes may be potential therapeutic targets for peritoneal carcinomatosis of gastric carcinoma.
Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice
Authors: Felipe G Serrano, Cheril Tapia-Rojas, Francisco J Carvajal, Juan Hancke, Waldo Cerpa, Nibaldo C Inestrosa
Journal: Molecular Neurodegeneration (2014)

Alzheimer’s disease (AD) is a neurodegenerative disorder in which the amyloid-β (Aβ) oligomers are a key factor in synaptic impairment and in spatial memory decline associated with neuronal dysfunction. This impairment includes synaptic failure associated with the loss of synaptic proteins that contribute to AD progression. Interestingly, the use of natural compounds is an emergent conceptual strategy in the search for drugs with therapeutic potentials for treating neurodegenerative disorders. In the present study, we report that andrographolide (ANDRO), which is a labdane diterpene extracted from Andrographis paniculata, increases slope of field excitatory postsynaptic potentials (fEPSP) in the CA1 region of hippocampal slices and inhibits long-term depression (LTD), protecting the long-term potentiation (LTP) against the damage induced by Aβ oligomers in vitro, most likely by inhibiting glycogen synthase kinase-3β (GSK-3β). Additionally, ANDRO prevents changes in neuropathology in two different age groups (7- and 12-month-old mice) of an AβPPswe/PS-1 Alzheimer’s model. ANDRO reduces the Aβ levels, changing the ontogeny of amyloid plaques in hippocampi and cortices in 7-month-old mice, and reduces tau phosphorylation around the Aβ oligomeric species in both age groups. Additionally, we observed that ANDRO recovers spatial memory functions that correlate with protecting synaptic plasticity and synaptic proteins in two different age groups. Our results suggest that ANDRO could be used in a potential preventive therapy during AD progression.
S-Adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial
Authors: Jose M Mato, Javier Cámara, Javier Fernández de Paz, Llorenç Caballería, Susana Coll, Antonio Caballero, Luisa García-Buey, Joaquín Beltrán, Vicente Benita, Joan Caballería, Ricard Solà, Ricardo Moreno-Otero, Félix Barrao, Antonio Martín-Duce, Jose A Correa, Albert Parés, Elena Barrao, Inmaculada García-Magaz, Jose Luis Puerta, Jorge Moreno, Gabrielle Boissard, Pablo Ortiz, Joan Rodés
Journal: Journal of Hepatology (1999)
Behavioral Intervention for Cancer Treatment Side Effects
Authors: W. H. Redd, G. H. Montgomery, K. N. DuHamel
Journal: JNCI Journal of the National Cancer Institute (2001)

The use of increasingly aggressive methods of cancer treatment during the last 20 years has brought clinical attention to the need for more effective management of pain, nausea, and other aversive side effects of state-of-the-art cancer therapy. One of the most promising approaches to effective management is nonpharmacologic intervention based on behavioral research and theory. The purpose of this review is to examine the effectiveness of behavioral intervention methods in the control of aversive side effects of cancer treatments. Fifty-four published studies using a variety of research designs were identified for review. Results indicated the following: 1) Behavioral intervention can effectively control anticipatory nausea and vomiting in adult and pediatric cancer patients undergoing chemotherapy; however, the evidence for the efficacy of behavioral intervention to control post-chemotherapy nausea and vomiting is less clear. 2) Behavioral intervention integrating several behavioral methods can ameliorate anxiety and distress associated with invasive medical treatments. 3) Although a variety of behavioral methods have been shown to reduce acute treatment-related pain, there is increasing evidence that these methods are not equally effective. Hypnotic-like methods, involving relaxation, suggestion, and distracting imagery, hold the greatest promise for pain management. Unfortunately, research is scant on the use of behavioral intervention to control prolonged pain associated with invasive medical procedures. It is clear that the application of behavioral theory and methods has an important place in the care of patients undergoing invasive cancer treatments.
Anti-apoptotic and growth-stimulatory functions of CK1 delta and epsilon in ductal adenocarcinoma of the pancreas are inhibited by IC261 in vitro and in vivo
Authors: C Brockschmidt, H Hirner, N Huber, T Eismann, A Hillenbrand, G Giamas, B Radunsky, O Ammerpohl, B Bohm, D Henne-Bruns, H Kalthoff, F Leithauser, A Trauzold, U Knippschild
Journal: Gut (2008)

<h3>Background:</h3> Pancreatic ductal adenocarcinomas (PDACs) are highly resistant to treatment due to changes in various signalling pathways. CK1 isoforms play important regulatory roles in these pathways. <h3>Aims:</h3> We analysed the expression levels of CK1 delta and epsilon (CK1δ/∊) in pancreatic tumour cells in order to validate the effects of CK1 inhibition by 3-[2,4,6-(trimethoxyphenyl)methylidenyl]-indolin-2-one (IC261) on their proliferation and sensitivity to anti-CD95 and gemcitabine. <h3>Methods:</h3> CK1δ/∊ expression levels were investigated by using western blotting and immunohistochemistry. Cell death was analysed by FACS analysis. Gene expression was assessed by real-time PCR and western blotting. The putative anti-tumoral effects of IC261 were tested <i>in vivo</i> in a subcutaneous mouse xenotransplantation model for pancreatic cancer. <h3>Results:</h3> We found that CK1δ/∊ are highly expressed in pancreatic tumour cell lines and in higher graded PDACs. Inhibition of CK1δ/∊ by IC261 reduced pancreatic tumour cell growth in vitro and in vivo. Moreover, IC261 decreased the expression levels of several anti-apoptotic proteins and sensitised cells to CD95-mediated apoptosis. However, IC261 did not enhance gemcitabine-mediated cell death either in vitro or in vivo. <h3>Conclusions:</h3> Targeting CK1 isoforms by IC261 influences both pancreatic tumour cell growth and apoptosis sensitivity in vitro and the growth of induced tumours in vivo, thus providing a promising new strategy for the treatment of pancreatic tumours.
Reprogramming Human Cancer Cells in the Mouse Mammary Gland
Authors: Karen M. Bussard, Corinne A. Boulanger, Brian W. Booth, Robert D. Bruno, Gilbert H. Smith
Journal: Cancer Research (2010)

The tissue microenvironment directs stem/progenitor cell behavior. Cancer cells are also influenced by the microenvironment. It has been shown that, when placed into blastocysts, cancer cells respond to embryonic cues and differentiate according to the tissue type encountered during ontological development. Previously, we showed that the mouse mammary gland was capable of redirecting adult mouse testicular and neural stem/progenitor cells toward a mammary epithelial cell fate during gland regeneration. Here, we report that human embryonal carcinoma cells proliferate and produce differentiated mammary epithelial cell progeny when mixed with mouse mammary epithelial cells and inoculated into the epithelium-free mammary fat pads of athymic nude mice. Fluorescence in situ hybridization confirmed the presence of human cell progeny in the mammary outgrowths for human centromeric DNA, as well as immunochemistry for human-specific breast epithelial cytokeratins and human-specific milk proteins in impregnated transplant hosts. It was found that the number of human cells increased by 66- to 660-fold during mammary epithelial growth and expansion as determined by human cytokeratin expression. All features found in primary outgrowths were recapitulated in the secondary outgrowths from chimeric implants. These results show that human embryonal carcinoma-derived progeny interact with mouse mammary cells during mammary gland regeneration and are directed to differentiate into cells that exhibit diverse mammary epithelial cell phenotypes. This is the first demonstration that human cells are capable of recognizing the signals generated by the mouse mammary gland microenvironment present during gland regeneration in vivo.
Modeling Inducible Human Tissue Neoplasia Identifies an Extracellular Matrix Interaction Network Involved in Cancer Progression
Authors: Jason A. Reuter, Susana Ortiz-Urda, Markus Kretz, John Garcia, Florence A. Scholl, Anna M.G. Pasmooij, David Cassarino, Howard Y. Chang, Paul A. Khavari
Journal: Cancer Cell (2009)
Mechanisms of Renal Release of Renin by Electrical Stimulation of the Brainstem in the Cat
Authors: DAVID RICHARDSON, ANDREA STELLA, GASTONE LEONETTI, ALBERTO BARTORELLI, ALBERTO ZANCHETTI
Journal: Circulation Research (1974)

Electrical stimulation of the dorsolateral pons for 5-minute periods in anesthetized cats produced a rise in blood pressure of 40%, a reduction in renal blood flow of 28%, and an increase in the rate of renin release (the product of renal plasma flow and the venoarterial difference of plasma renin activity) of more than 100% in intact kidneys. Comparison of an intact kidney with the contralateral denervated one showed that denervation abolished the decrease in renal blood flow and the increase in renin release induced by pontine stimulation. Infusion of phenoxybenzamine into an otherwise intact kidney prevented the decrease in renal blood flow on that side, but brain-induced renin release was at least equal to that from the contralateral kidney in which the vasomotor response remained unchanged. Treatment of the animal with intravenously administered propranolol (1.3-3.0 mg/kg) abolished any rise in renin release, although propranolol accentuated the reduction in renal blood flow during stimulation of the brainstem. We concluded that the increased renal release of renin induced by electrical stimulation of a pressor area of the brainstem was dependent on intact renal nerves and on mechanisms blocked by propranolol but was not dependent on changes in renal blood flow or on renal alpha receptors.