tbuckley/cabot-search huggingface dataset:
Autologous haematopoietic stem cell transplantation without CD34+ cell selection in refractory Crohn's disease
Authors: A Cassinotti, C Annaloro, S Ardizzone, F Onida, A D. Volpe, M Clerici, P Usardi, S Greco, G Maconi, G B. Porro, G L. Deliliers
Journal: Gut (2007)

<h3>Objectives:</h3> Autologous haematopoietic stem cell transplantation (HSCT) with CD34<sup>+</sup> cell selection has recently been used in the treatment of refractory Crohn's disease, showing good safety and promising efficacy. We investigated the safety and efficacy of HSCT with unselected peripheral blood stem cells (PBSCs) in moderate–severe refractory Crohn's disease. <h3>Patients:</h3> Four patients (three male, one female; age range 26–45 years) with active moderate–severe Crohn's disease (median Crohn's Disease Activity Index (CDAI) 319, range 272–345), refractory or intolerant to multiple drugs including infliximab, were enrolled. <h3>Interventions:</h3> Unselected PBSCs were collected after mobilisation with cyclophosphamide (CTX) 1.5 g/m2 and granulocyte-colony stimulating factor (G-CSF) 10 μg/kg. The conditioning regimen included CTX 50 mg/kg on days −5 to −2 and rabbit anti-thymocyte globulin (ATG) 2.5 mg/kg on days −4 to −2. <h3>Main outcome measures:</h3> Primary endpoints were toxicity and clinical remission (CDAI&lt;150) at 3 months. Secondary endpoints were clinical and endoscopic response at 3 months and toxicity, clinical and endoscopic remission at 12 months. <h3>Results:</h3> No improvement or slight deterioration was observed following mobilisation (median CDAI 339, range 258–404). At the third month, the primary endpoint of clinical remission was achieved in all patients, with a median CDAI of 91 (range 56–102), and complete endoscopic remission was achieved in 2/3 patients. After a median follow-up of 16.5 months, 3/4 patients maintained both clinical and endoscopic remission, despite withdrawal of all drugs, and complete fistula closure was observed in all affected patients. No deaths or life-threatening infection occurred. Unexpected adverse events included a perianal abscess after mobilisation in one patient, pleural and pericardial effusions in another and BK virus-related macrohaematuria in another, all rapidly resolved with conservative treatment. <h3>Conclusion:</h3> Autologous HSCT with unselected PBSC appears to be safe and can induce and maintain remission in previously refractory Crohn's disease patients.
Requirement for non-T cells in the generation of cytotoxic T lymphocytes in vitro. I. Use of nude mice as source of non-T cells.
Authors: R M Schilling, R A Phillips, R G Miller
Journal: The Journal of Experimental Medicine (1976)

The ability of small numbers of LN cells to produce cytotoxic lymphocytes on in vitro culture with allogeneic stimulator cells is greatly augmented by the addition of spleen cells from athymic nude mice. The possibility that the synergism is a result of improved culture conditions or a "feeder effect" is excluded. All cytotoxic cells found in these cultures are shown to be T cells and to arise from precursors contained in the LN-cell component. The nude spleen cell component appears to be providing a required non-T cell which has been lost from the LN component through dilution. Synergism between the two components can occur whether they are syngeneic or allogeneic provided that both can recognize the same alloantigens in the stimulator population.
Long-term result after operative correction of funnel chest
Authors: S. Borgeskov, D. Raahave
Journal: Thorax (1971)

During the last decades it has been commonly accepted that funnel chest is such a serious cosmetic handicap that it deserves correction for this reason alone. A group of patients with this deformity, operated upon by the method of Paltia (transsternal fixation with metal struts), was re-examined 5 to 10 years postoperatively. In more than 50% of the cases the immediate acceptable cosmetic result had disappeared in contrast to the satisfaction expressed by almost all the patients. Because of the high incidence of recurrence and because of various risks involved in this operation, the authors do not advocate its performance.
Effect of stress on oesophageal motor function in normal subjects and in patients with the irritable bowel syndrome.
Authors: E E Soffer, P Scalabrini, C E Pope, D L Wingate
Journal: Gut (1988)

Stress can modulate the motor function of the stomach, small bowel, and colon in healthy subjects, and of the small bowel and colon in patients with the irritable bowel syndrome (IBS). The effect of stress on oesophageal motility in eight healthy subjects and in eight IBS patients was studied, using two pressure transducers positioned just above the lower oesophageal sphincter and 5 cm proximally. Stressors were: a video arcade game, delayed audio feedback, and hand immersion in cold water. Each stress period was followed by five swallows of water. Frequency and amplitude of oesophageal contractions and the number of simultaneous and multipeaked contractions were manually counted for each stress period and compared to the preceding rest period. Frequency of contractions (per minute) tended to decrease during stress periods, but achieved significance only with the video arcade game in the control group (2.0 (0.6) v 1.2 (0.4); p less than 0.01). No other trend was evident in either control or IBS patients. No abnormalities of oesophageal body function were recorded in IBS patients either in basal conditions, or under stress. Unlike the more complex motor programmes elsewhere in the gut, the preprogrammed nature of oesophageal peristalsis is not modulated by stress.
Signaling Pathways Involved in Adenosine Triphosphate-Induced Endothelial Cell Barrier Enhancement
Authors: Irina A. Kolosova, Tamara Mirzapoiazova, Djanybek Adyshev, Peter Usatyuk, Lewis H. Romer, Jeffrey R. Jacobson, Viswanathan Natarajan, David B. Pearse, Joe G.N. Garcia, Alexander D. Verin
Journal: Circulation Research (2005)

Endothelial barrier dysfunction caused by inflammatory agonists is a frequent underlying cause of vascular leak and edema. Novel strategies to preserve barrier integrity could have profound clinical impact. Adenosine triphosphate (ATP) released from endothelial cells by shear stress and injury has been shown to protect the endothelial barrier in some settings. We have demonstrated that ATP and its nonhydrolyzed analogues enhanced barrier properties of cultured endothelial cell monolayers and caused remodeling of cell–cell junctions. Increases in cytosolic Ca 2+ and Erk activation caused by ATP were irrelevant to barrier enhancement. Experiments using biochemical inhibitors or siRNA indicated that G proteins (specifically G αq and G αi2 ), protein kinase A (PKA), and the PKA substrate vasodilator-stimulated phosphoprotein were involved in ATP-induced barrier enhancement. ATP treatment decreased phosphorylation of myosin light chain and specifically activated myosin-associated phosphatase. Depletion of G αq with siRNA prevented ATP-induced activation of myosin phosphatase. We conclude that the mechanisms of ATP-induced barrier enhancement are independent of intracellular Ca 2+ , but involve activation of myosin phosphatase via a novel G-protein–coupled mechanism and PKA.
A Nasal Cannula Can Be Used to Treat Obstructive Sleep Apnea
Authors: Brian M. McGinley, Susheel P. Patil, Jason P. Kirkness, Philip L. Smith, Alan R. Schwartz, Hartmut Schneider
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Obstructive sleep apnea syndrome is due to upper airway obstruction and is associated with increased morbidity. Although continuous positive airway pressure efficaciously treats obstructive apneas and hypopneas, treatment is impeded by low adherence rates.
Reversing Hormone Resistance: Have We Found the Golden Key?
Authors: Hope S. Rugo, Sara Keck
Journal: Journal of Clinical Oncology (2012)

Hormone receptors are present in the majority of both early- and late-stage breast cancers, with expression found in approximately 65% to 70% of metastatic tumors. Despite the availability of a number of effective hormone therapies, resistance develops in a subset of earlystage tumors and in almost all tumors in the advanced setting. In addition, a subset of hormone receptor–positive tumors are primarily resistant to hormone therapies. The search for mechanisms to reverse resistance has focused on inhibiting pathways that are known to be upregulated in the setting of progressive disease. 1-3 Improvements in response and progression-free survival (PFS) that were seen with the addition of human epidermal growth factor receptor 2 (HER2)– targeted therapy to first-line aromatase inhibitors in patients with HER2-positive, hormone receptor–positive metastatic breast cancer represented the first clear indication that targeting growth factor receptor pathways could be an effective approach to reversing resistance, 4,5 and added additional validity to preclinical models that predicted this effect. 3 However, only approximately 8% to 10% of breast cancers are both HER2- and hormone receptor–positive, so the search for other approaches remains a critical research and clinical question. Phosphatidyl inositol 3-kinase (PI3K) is the most frequently altered pathway in breast cancer, with both mutations and amplifications of the encoding genes. 6 This pathway mediates a number of critical cellular processes including cell growth, proliferation, and survival. Mammalian target of rapamycin (mTOR) is a signal transduction kinase in the PI3K pathway that exists in two multiprotein complexes, mTOR complexes 1 and 2 (mTORC1 and mTORC2; Fig 1). mTORC1 consists of mTOR that is associated with raptor (regulatory-associated protein of mTOR) and is downstream of AKT. In contrast, mTORC2 is associated with rictor (rapamycin-insensitive
Association of the <i>KIAA0319</i> Dyslexia Susceptibility Gene With Reading Skills in the General Population
Authors: Silvia Paracchini, Colin D. Steer, Lyn-Louise Buckingham, Andrew P. Morris, Susan Ring, Thomas Scerri, John Stein, Marcus E. Pembrey, Jiannis Ragoussis, Jean Golding, Anthony P. Monaco
Journal: American Journal of Psychiatry (2008)

Objective: The authors previously identified a haplotype on chromosome 6p22 defined by three single-nucleotide polymorphisms (SNPs) that was associated with dyslexia (reading disability) in two independent samples of families that included at least one sibling with severe reading impairment. The authors also showed that this haplotype is associated with a reduction in expression of the KIAA0319 gene. In addition, a completely independent study detected an association between KIAA0319 markers and reading disability. In the current study, the authors tested whether the KIAA0319 gene influences reading skills in the general population, rather than having an effect restricted to reading disability. Method: The authors genotyped four SNPs that previously showed association with reading disability in the population of 7–9-year-old children in the Avon Longitudinal Study of Parents and Children (ALSPAC), a large longitudinal cohort for which reading-related phenotypes were available for more than 6,000 individuals. The authors conducted quantitative analysis for both single markers and haplotypes. Results: The rs2143340 SNP, which effectively tags the three-SNP risk haplotype, was significantly associated with a test for reading ability. The risk haplotype itself also showed association with poor reading performance, and as in previous research, the association was stronger when the analysis was controlled for IQ. Conclusions: These results both support a role of the KIAA0319 gene in the development of dyslexia and suggest that this gene influences reading ability in the general population. Moreover, the data implicate the three-SNP haplotype and its tagging SNP rs2143340 as genetic risk factors for poor reading performance.
Androgen Receptor Signaling Regulates DNA Repair in Prostate Cancers
Authors: William R. Polkinghorn, Joel S. Parker, Man X. Lee, Elizabeth M. Kass, Daniel E. Spratt, Phillip J. Iaquinta, Vivek K. Arora, Wei-Feng Yen, Ling Cai, Deyou Zheng, Brett S. Carver, Yu Chen, Philip A. Watson, Neel P. Shah, Sho Fujisawa, Alexander G. Goglia, Anuradha Gopalan, Haley Hieronymus, John Wongvipat, Peter T. Scardino, Michael J. Zelefsky, Maria Jasin, Jayanta Chaudhuri, Simon N. Powell, Charles L. Sawyers
Journal: Cancer Discovery (2013)

Abstract We demonstrate that the androgen receptor (AR) regulates a transcriptional program of DNA repair genes that promotes prostate cancer radioresistance, providing a potential mechanism by which androgen deprivation therapy synergizes with ionizing radiation. Using a model of castration-resistant prostate cancer, we show that second-generation antiandrogen therapy results in downregulation of DNA repair genes. Next, we demonstrate that primary prostate cancers display a significant spectrum of AR transcriptional output, which correlates with expression of a set of DNA repair genes. Using RNA-seq and ChIP-seq, we define which of these DNA repair genes are both induced by androgen and represent direct AR targets. We establish that prostate cancer cells treated with ionizing radiation plus androgen demonstrate enhanced DNA repair and decreased DNA damage and furthermore that antiandrogen treatment causes increased DNA damage and decreased clonogenic survival. Finally, we demonstrate that antiandrogen treatment results in decreased classical nonhomologous end-joining. Significance: We demonstrate that the AR regulates a network of DNA repair genes, providing a potential mechanism by which androgen deprivation synergizes with radiotherapy for prostate cancer. Cancer Discov; 3(11); 1245–53. ©2013 AACR. See related commentary by Bartek et al., p. 1222 This article is highlighted in the In This Issue feature, p. 1207
Identification of pemphigus-like antigens expressed by SCaBER cells
Authors: E. ACOSTA, L. IVANYI
Journal: British Journal of Dermatology (1985)

Indirect immunofluorescence revealed the presence of pemphigus-like antigenic activity on SCaBER cell monolayers after incubation with sera from patients with pemphigus vulgaris. In contrast, no fluorescence was observed after incubation of the cells with sera from patients with bullous pemphigoid, systemic lupus erythematosus or healthy individuals. In order to identify this pemphigus-like antigen, the SCaBER cell membrane proteins were solubilized in non-ionic detergent, separated according to their molecular weight by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and electrophoretically transferred to nitrocellulose sheets. After incubation with pemphigus serum followed by 125 I-radiolabelled goat anti-human IgG, autoradiography revealed pemphigus antibody binding activity in the 105 Kd region in electrophoretograms of the unreduced SCaBER cell membrane extracts. This pemphigus-like antigen was isolated by affinity chromatography on the Sepharose-linked IgG fraction of sera from patients with pemphigus vulgaris.
Neutrophil CD64 expression: distinguishing acute inflammatory autoimmune disease from systemic infections
Authors: E Allen
Journal: Annals of the Rheumatic Diseases (2002)

Background: Common bacterial and opportunistic infections are a major cause of mortality in patients who are immunosuppressed owing to treatment with corticosteroids or cytotoxic drugs. Common laboratory tests for infection lack sensitivity and specificity. One of the new generation of tests to detect early systemic infections measures the up regulation of an Fc receptor (Fcγ R1, or CD64) on neutrophils. The Fc receptors on white blood cells are very important for effective phagocytosis of bacteria and are up regulated during an infection. Objective: To measure the clinical usefulness of quantitative CD64 measurements to differentiate between systemic infection and active autoimmune inflammation in an ongoing study. Methods: Patients with systemic infection (n=27), active autoimmune inflammatory disease (n=44), vasculitis (n=5), and controls (n=20) were studied for neutrophil CD64 expression using monoclonal antibodies and flow cytometry. Results: The median (interquartile range (IQR)) CD64 expression in patients with active inflammatory disease and systemic infection was 907.5 (586–1550) and 3647 (2380–6642), respectively (p&lt;0.0001). The median (IQR) CD64 expression in control patients (osteoarthritis and fibromyalgia) was 505 (359–599). The sensitivity and specificity of CD64 expression on neutrophils to diagnose systemic infection (using a cut off value of 2000) was 85% and 91%, respectively. Conclusion: These results indicate that quantitative measurement of CD64 can distinguish between systemic infection and the flare of autoimmune diseases.
The United States of Repression
Authors: Sadia Najmi, Daniel M. Wegner
Journal: Behavioral and Brain Sciences (2006)

Erdelyi's account of thought suppression , which he equates with the Freudian construct of repression , is that it is mostly successful, and that it undermines memory for the suppressed material. Erdelyi has neglected to consider evidence from two decades of research on suppression which renders both these claims invalid. Contrary to Erdelyi's thesis, suppression often enhances the accessibility of unwanted material.
Observations of unprecedented remissions following novel treatment for acute leukemia in children in 1948
Authors: Peter D Spain, Nina Kadan-Lottick
Journal: Journal of the Royal Society of Medicine (2012)

Half a century ago, a diagnosis of leukemia in a child was considered a death sentence. Today, approximately 85% of children diagnosed with this once fatal disease are cured.1,2 The discovery that ushered in this dramatically transformed outlook was the observation by Sidney Farber (1903–1973) and his colleagues in Boston in 1948 that drugs that acted against the vitamin folic acid could produce remissions in children with acute leukemia.3 While carefully controlled studies were required to develop therapeutic regimens developed from these initial observations,4,5 the Farber article is featured in the James Lind Library because it is an example of a treatment effect that is so dramatic that bias can be confidently ruled out as an explanation for the observations.6 What led to the landmark findings in 1948, and what evidence was published subsequently confirming that a major advance in treatment had been discovered?
Altered Dynamics of Action Potential Restitution and Alternans in Humans With Structural Heart Disease
Authors: Marcus L. Koller, Sebastian K.G. Maier, Anna R. Gelzer, Wolfgang R. Bauer, M. Meesmann, Robert F. Gilmour
Journal: Circulation (2005)

Restitution kinetics and alternans of ventricular action potential duration (APD) have been shown to be important determinants of cardiac electrical stability. In this study, we tested the hypothesis that APD restitution and alternans properties differ between normal and diseased human ventricular myocardium.Monophasic action potentials were recorded from the right ventricular septum in 24 patients with structural heart disease (SHD) and in 12 patients without SHD. Standard and dynamic restitution relations were constructed by plotting APD as a function of the preceding diastolic interval. The dynamic restitution relation of both groups showed a steeply sloped segment at short diastolic intervals that was associated with the occurrence of APD alternans. Patients with SHD had a wider diastolic interval range over which APD alternans was present (mean+/-SEM 68+/-11 versus 12+/-2 ms) and showed an earlier onset (168+/-7 versus 225+/-4 bpm) and an increased magnitude (20+/-2 versus 11+/-2 ms) of APD alternans compared with patients without SHD. The occurrence of APD alternans during induced ventricular tachycardia (6 episodes) and during rapid pacing could be derived from the dynamic restitution function.There are marked differences in the dynamics of APD restitution and alternans in the ventricular myocardium of patients with SHD compared with patients without SHD. These differences may contribute importantly to cardiac electrical instability in diseased human hearts and may represent a promising target for antiarrhythmic substrate modification.
Monocytes in heart failure: relationship to a deteriorating immune overreaction or a desperate attempt for tissue repair?
Authors: S. Apostolakis, G. Y.H. Lip, E. Shantsila
Journal: Cardiovascular Research (2009)

Monocytes play an important role in immune defence, inflammation, and tissue remodelling. Nevertheless, the role of monocytes in cardiovascular disease is obscure. Indeed, monocytes infiltrate dysfunctional tissue and augment tissue damage and are actively involved in tissue regeneration and healing. In support of the latter, recent studies have provided data on the functional and structural plasticity of monocytes. Monocytes are also actively involved in processes associated with tissue regeneration such as angiogenesis and vasculogenesis, either by producing pro-angiogenic factors or even by evolving to structural components of the vascular wall. This review article provides an overview on whether monocytes represent deteriorating immune overreaction in heart failure (HF), or a desperate attempt for tissue repair or physiological compensation in the failing heart. Perhaps, it is time to reconsider our attitude towards monocytes and consider more 'monocyte activation' rather than 'monocyte suppression' as a potential therapeutic target in HF.
A genetic test which can be used to diagnose adult-type hypolactasia in children
Authors: H Rasinpera
Journal: Gut (2004)

Adult-type hypolactasia (primary lactose malabsorption) affects most of world's human population and limits the use of fresh milk due to lactose intolerance. The diagnosis of adult-type hypolactasia has been difficult to establish because of unsatisfactory diagnostic methods. C/T(-13910) single nucleotide polymorphism residing 13910 base pairs from the 5' end of the lactase gene has been shown to be associated with lactase persistence. The aim of the study was to assess the applicability of the C/T(-13910) variant as a diagnostic test for adult-type hypolactasia during childhood.
Prostaglandins, Glucose Homeostasis, and Diabetes Mellitus
Authors: R. Paul Robertson
Journal: Annual Review of Medicine (1983)

Prostaglandins of the E series are implicated as regulators of glucose homeostasis because of their effects on glucose production and secretion of insulin and glueagon. PGE is postulated to play a role in the pathophysiology of insulin secretion in adult-onset (Type II) diabetes mellitus. Evidence supporting this hypothesis includes the demonstration that PGE inhibits glucose-induced acute insulin responses in normal humans. Moreover, drugs that inhibit synthesis of PGE improve abnormal insulin secretion in human subjects with Type II diabetes mellitus.
Somatic Cell Cloning
Authors: Jorge A. Piedrahita, Bashir Mir, Scott Dindot, Shawn Walker
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. With the increasing difficulties associated with meeting the required needs for organs used in transplantation, alternative approaches need to be considered. These include the use of stem cells as potential sources of specialized cells, the ability to transdifferentiate cell types in culture, and the development of complete organs that can be used in humans. All of the above goals will require a complete understanding of the factors affecting cell differentiation and nuclear reprogramming. To make this a reality, however, techniques associated with cloning and genetic modifications in somatic cells need to be continued to be developed and optimized. This includes not only an enhancement of the rate of homologous recombination in somatic cells, but also a thorough understanding of the nuclear reprogramming process taking place during nuclear transfer. The understanding of this process is likely to have an effect beyond the area of nuclear transfer and assist with better methods for transdifferentiation of mammalian cells.