tbuckley/cabot-search huggingface dataset:
Oesophageal motor responses to gastro-oesophageal reflux in healthy controls and reflux patients
Authors: A Anggiansah, G Taylor, R E K Marshall, N F Bright, W A Owen, W J Owen
Journal: Gut (1997)

To compare oesophageal motor responses to gastro-oesophageal reflux (GOR) in 16 healthy controls (group 1) and 25 reflux patients, 15 without (group 2) and 10 with (group 3) oesophagitis.All subjects underwent 24 hour ambulatory oesophageal pH measurements (5 cm above the lower oesophageal sphincter (LOS)) combined with pressure monitoring (5, 10, and 15 cm above the LOS for oesophageal body motility and 27 cm above the LOS for voluntary swallow detection). Contraction patterns (peristaltic, simultaneous, isolated, mixed type, and non-transmitted swallows) and peristaltic contraction wave characteristics (amplitude, duration, and velocity) during GOR were compared in the three groups.The average number of motor activities per minute was significantly higher in group 1 (p < 0.05). In all groups, the most common motor contraction pattern was peristaltic. The percentage of peristaltic activity per subject was significantly higher in group 1 (p < 0.05). There were no significant differences in other contraction patterns among the three groups (p > 0.05). Of the peristaltic contraction wave characteristics there were no significant differences in any parameters (amplitude, duration, and velocity) among the three groups (p > 0.05). The average pH increment in response to motor activities was significantly higher in group 1 (p < 0.05).Motor responses to GOR were found to be predominantly primary peristaltic in all groups. During GOR, reflux patients have less frequent activity, a smaller proportion of activity is peristaltic, and the average pH increment in response to motor activities is reduced compared with controls.
Arg–Gly–Asp (RGD)-containing peptides increase soluble guanylate cyclase in contractile cells
Authors: M DIEZMARQUES, M RUIZTORRES, M GRIERA, S LOPEZONGIL, M SAURA, D RODRIGUEZPUYOL, M RODRIGUEZPUYOL
Journal: Cardiovascular Research (2005)

Alterations in NO/cGMP signaling have been associated with vascular dysfunction. Here, we tested whether peptides containing arginine-glycine-aspartic acid (RGD) motifs, commonly found on the binding sites of extracellular matrix to integrins, could increase the expression and function of soluble guanylate cyclase (sGC) in human mesangial cell (HMC), and human aortic smooth muscle (HASMC) cells.Arginine-glycine-aspartic acid-serine (RGDS) promoted an up-regulation in the sGC beta1 subunit steady-state level, both in HMC and HASMC, in a time- and dose-dependent manner. The cellular effects of RGDS-stimulation of sGC expression was an enhanced cellular response to sodium nitroprusside, resulting in elevated cGMP levels and vasodilator-stimulated phosphoprotein (VASP) phosphorylation in both kinds of cells, and an increased NO relaxing effect on cells precontracted with H(2)O(2) or Angiotensin II. Moreover, RGDS was able to restore the sGC levels that had been previously decreased by long term exposure to NO donors. RGDS effects on sGC regulation were due to the specific interaction with alpha(5)beta(1) integrin. To investigate the intracellular mechanisms activated after RGDS cell treatment, pharmacological kinase inhibitors were used. The effect of RGDS on sGC protein content was completely abolished by treating the cells with c-Jun N-terminal kinase (JNK) inhibitors. In addition, c-fos and c-jun were found in the cell nuclei after RGDS treatment, suggesting that the RGDS effect could be mediated by the AP-1 transcription factor.Results provide evidence of a mechanism able to increase the sGC protein content linked to increased activity in contractile cells, not only in basal conditions, but also after the down-regulation of the receptor by its own substrate. Elucidation of this novel mechanism provides a rationale for future pharmacotherapy in certain vascular diseases.
Raised immunoglobulin concentrations in bronchoalveolar lavage fluid of healthy granite workers.
Authors: W J Calhoun, J W Christman, W B Ershler, W G Graham, G S Davis
Journal: Thorax (1986)

Immunoglobulin concentrations and lymphocyte counts were determined in bronchoalveolar fluid obtained from nine symptomless, healthy, non-smoking granite workers (mean age 45.6, range 22-56 years) and nine normal, non-smoking, non industrial controls (mean age 22.8, range 21-32 years). The proteins were measured in unconcentrated lavage fluid by means of a solid phase, enzyme linked immunosorbent assay. IgG and IgA concentrations were three times greater in lavage fluid from granite workers than the samples from non-industrial controls (p less than 0.02). Eight of nine normal volunteers (89%) had no detectable IgM (less than 30 ng/ml) in the lavage fluid whereas eight of nine (89%) granite workers had detectable IgM (chi 2 = 8, p less than 0.01). Lymphocyte counts in lavage fluid from the workers were significantly greater (15.5%) than control counts (5.6%; p less than 0.05). The normal albumin concentration suggests that differences in permeability do not account for all of the increased immunoglobulin concentrations found in granite workers9 lavage fluid and that some immunoglobulin is locally synthesised. It is concluded that occupational exposure to granite dust is associated with an increased proportion of lymphocytes and an increased concentration of immunoglobulin in lavage fluid that may reflect a subclinical immune inflammatory response.
MB-10 * GSK-3 PROMOTES PROLIFERATION DURING POSTNATAL CEREBELLAR DEVELOPMENT AND MAY BE TARGETED IN MEDULLOBLASTOMA THERAPY
Authors: J. Ocasio, T. Gershon
Journal: Neuro-Oncology (2015)

In light of prior studies showing that GSK-3 is required to prevent overgrowth of cerebral neural progenitors, we examined whether deletion of GSK-3 in the cerebellum would produce hyperplasia and support medulloblastoma tumorigenesis. GSK-3 regulates diverse intracellular processes, including signaling through Wnt and N-myc, which have both been implicated in tumorigenesis. We deleted both isoforms of GSK-3 conditionally in the cerebellum by crossing GSKα -/-:GSKβ f/f mice with the Math1-cre transgenic line. We found that GSK-3 deletion induced marked hypoproliferation in the cerebellum, contrary to the hyperproliferation seen when GSK in deleted in cortical progenitors. Transcription analysis by microarray revealed that hypoplasia was preceded by a strong activation of WNT signaling. Deleting GSK-3 in medulloblastoma-prone SmoM2 mice markedly reduced tumor growth. Ongoing studies will determine if WNT signaling is activated in GSK-deleted tumors and may mediate the reduced growth. Our data show that the predominant effect of GSK-3 during cerebellar development and medulloblastoma formation is to promote growth, and that disruption of GSK-3 function may exert a significant restriction on tumor growth.
Overestimation of Left Ventricular Volume by the Indicator Dilution Technique
Authors: Richard A. Carleton, Allen F. Bowyer, John S. Graettinger
Journal: Circulation Research (1966)

The applicability of the indicator dilution method to the measurement of left ventricular volume has been studied. When compared with angiocardiographic measurements, the dilution technique overestimates volume by an average of 52 and 91% in end diastole and end systole respectively. Studies which demonstrated more rapid indicator washout from the outflow than from the apical portion of human and canine left ventricles suggest that faulty intraventricular indicator dispersion is the major cause of the volume over-estimates yielded by the dilution method. Procedures designed to alter ventricular size by altering venous return produced parallel changes in ventricular circumference and in ventricular indicator washout volume. The indicator dilution method does not provide a measure of left ventricular volume, but may, in carefully designed studies, yield an index of changes in ventricular size.
Treatment of Causalgia
Authors: Ray J. Defalque
Journal: JAMA (1969)

We present here a case of causalgia which has intrigued us by its bizarre course and long duration and has taught us a lesson that we want to share. The patient was a 74-year-old veteran; in 1918 he had been hit near the left elbow by shrapnel which had slightly damaged bones, muscles, and the median nerve, and severed his ulnar nerve. The latter nerve was successfully grafted four months later. In spite of some deformity and limitation of movement, the left arm regained good function, and the patient led an active life as a farmer. A few weeks after surgery, a throbbing, burning pain of the whole left upper extremity, especially along the ulnar side, developed. The patient sought no help, kept on working, and over the years the pain eventually subsided. It suddenly recurred in 1956, and rapidly progressed to the point where it kept the patient awake
Ethical Challenges and Interpretive Difficulties with Non-Clinical Applications of Pediatric fMRI
Authors: Andrew Fenton, Letitia Meynell, Françoise Baylis
Journal: The American Journal of Bioethics (2009)

In this article, we critically examine some of the ethical challenges and interpretive difficulties with possible future non-clinical applications of pediatric fMRI with a particular focus on applications in the classroom and the courtroom – two domains in which children come directly in contact with the state. We begin with a general overview of anticipated clinical and non-clinical applications of pediatric fMRI. This is followed by a detailed analysis of a range of ethical challenges and interpretive difficulties that trouble the use of fMRI and are likely to be especially acute with non-clinical uses of the technology. We conclude that knowledge of these challenges and difficulties should influence policy decisions regarding the non-clinical uses of fMRI. Our aim is to encourage the development of future policies prescribing the responsible use of this neuroimaging technology as it develops both within and outside the clinical setting.
Medical Student Exposure to Drug Company Interactions
Authors: Michael Eisman
Journal: JAMA (2006)

1. de Gruijl FR, van Kranen HJ, Mullenders LH. UV-induced DNA damage, repair, mutations and oncogenic pathways in skin cancer. J Photochem Photobiol B. 2001; 63:19-27. 2. Dennis LK, Beane Freeman LE, VanBeek MJ. Sunscreen use and the risk for melanoma: a quantitative review. Ann Intern Med. 2003;139:966-978. 3. Marks R, Staples M, Giles GG. Trends in non-melanocytic skin cancer treated in Australia: the second national survey. Int J Cancer. 1993;53:585-590. 4. Marcil I, Stern RS. Risk of developing a subsequent nonmelanoma skin cancer in patients with a history of nonmelanoma skin cancer: a critical review of the literature and meta-analysis. Arch Dermatol. 2000;136:1524-1530.
Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib
Authors: F.R. Hirsch, M. Varella-Garcia, F. Cappuzzo, J. McCoy, L. Bemis, A.C. Xavier, R. Dziadziuszko, P. Gumerlock, K. Chansky, H. West, A.F. Gazdar, L. Crino, D.R. Gandara, W.A. Franklin, P.A. Bunn
Journal: Annals of Oncology (2007)
Creatine Phosphate Consumption and the Actomyosin Crossbridge Cycle in Cardiac Muscles
Authors: Ozgur Ogut, Frank V. Brozovich
Journal: Circulation Research (2003)

To investigate the regulation of the actomyosin crossbridge cycle in cardiac muscles, the effects of ATP, ADP, Pi, and creatine phosphate (CP) on the rate of force redevelopment (ktr) were measured. We report that CP is a primary determinant in controlling the actomyosin crossbridge cycling kinetics of cardiac muscles, because a reduction of CP from 25 to 2.5 mmol/L decreased ktr by 51% despite the presence of 5 mmol/L MgATP. The effects of CP on ktr were not a reflection of reduced ATP or accumulated ADP, because lowering ATP to 1 mmol/L or increasing ADP to 1 mmol/L did not significantly decrease ktr. Therefore, the effect of CP on the actomyosin crossbridge cycle is proposed to occur through a functional link between ADP release from myosin and its rephosphorylation by CP–creatine kinase to regenerate ATP. In activated fibers, the functional link influenced the kinetics of activated crossbridges without affecting the aggregate number of force-generating crossbridges. This was demonstrated by the ability of CP to affect ktr in maximally and submaximally activated fibers without altering the force per cross-sectional area. The data also confirm the important contribution of strong binding crossbridges to cardiac muscle activation, likely mediated by cooperative recruitment of adjacent crossbridges to maximize force redevelopment against external load. These data provide additional insight into the role of CP during pathophysiological conditions such as ischemia, suggesting that decreased CP may serve as a primary determinant in the observed decline of dP/dt.
Auscultation of the lung: past lessons, future possibilities.
Authors: R L Murphy
Journal: Thorax (1981)

Review of the history of auscultation of the lung reveals few scientific investigations. The majority of these have led to inconclusive results. The mechanism of production of normal breath sounds remains uncertain. Hypotheses for the generation of adventitious sounds are unproven. Advances in instrumentation for lung sound recording and analysis have provided little of clinical value. There has been a recent resurgence of interest in lung sounds. Space-age technology has improved methodology for sonic analysis significantly. Lung sounds are complex signals that probably reflect regional lung pathophysiology. If they were understood more clearly important non-invasive diagnostic tools could be devised and the value of clinical auscultation could be improved. A multidisciplinary effort will be required to achieve this.
Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKBβ
Authors: Robert S. Garofalo, Stephen J. Orena, Kristina Rafidi, Anthony J. Torchia, Jeffrey L. Stock, Audrey L. Hildebrandt, Timothy Coskran, Shawn C. Black, Dominique J. Brees, Joan R. Wicks, John D. McNeish, Kevin G. Coleman
Journal: Journal of Clinical Investigation (2003)

The serine/threonine kinase Akt/PKB plays key roles in the regulation of cell growth, survival, and metabolism. It remains unclear, however, whether the functions of individual Akt/PKB isoforms are distinct. To investigate the function of Akt2/PKBβ, mice lacking this isoform were generated. Both male and female Akt2/PKBβ-null mice exhibit mild growth deficiency and an age-dependent loss of adipose tissue or lipoatrophy, with all observed adipose depots dramatically reduced by 22 weeks of age. Akt2/PKBβ-deficient mice are insulin resistant with elevated plasma triglycerides. In addition, Akt2/PKBβ-deficient mice exhibit fed and fasting hyperglycemia, hyperinsulinemia, glucose intolerance, and impaired muscle glucose uptake. In males, insulin resistance progresses to a severe form of diabetes accompanied by pancreatic β cell failure. In contrast, female Akt2/PKBβ-deficient mice remain mildly hyperglycemic and hyperinsulinemic until at least one year of age. Thus, Akt2/PKBβ-deficient mice exhibit growth deficiency similar to that reported previously for mice lacking Akt1/PKBα, indicating that both Akt2/PKBβ and Akt1/PKBα participate in the regulation of growth. The marked hyperglycemia and loss of pancreatic β cells and adipose tissue in Akt2/PKBβ-deficient mice suggest that Akt2/PKBβ plays critical roles in glucose metabolism and the development or maintenance of proper adipose tissue and islet mass for which other Akt/PKB isoforms are unable to fully compensate.
Cd40-Independent Pathways of T Cell Help for Priming of Cd8+ Cytotoxic T Lymphocytes
Authors: Zhengbin Lu, Lingxian Yuan, Xianzheng Zhou, Eduardo Sotomayor, Hyam I. Levitsky, Drew M. Pardoll
Journal: The Journal of Experimental Medicine (2000)

In many cases, induction of CD8+ CTL responses requires CD4+ T cell help. Recently, it has been shown that a dominant pathway of CD4+ help is via antigen-presenting cell (APC) activation through engagement of CD40 by CD40 ligand on CD4+ T cells. To further study this three cell interaction, we established an in vitro system using dendritic cells (DCs) as APCs and influenza hemagglutinin (HA) class I and II peptide–specific T cell antigen receptor transgenic T cells as cytotoxic T lymphocyte precursors and CD4+ T helper cells, respectively. We found that CD4+ T cells can provide potent help for DCs to activate CD8+ T cells when antigen is provided in the form of either cell lysate, recombinant protein, or synthetic peptides. Surprisingly, this help is completely independent of CD40. Moreover, CD40-independent CD4+ help can be documented in vivo. Finally, we show that CD40-independent T cell help is delivered through both sensitization of DCs and direct CD4+–CD8+ T cell communication via lymphokines. Therefore, we conclude that CD4+ help comprises at least three components: CD40-dependent DC sensitization, CD40-independent DC sensitization, and direct lymphokine-dependent CD4+–CD8+ T cell communication.
β-Catenin Promotes Regulatory T-cell Responses in Tumors by Inducing Vitamin A Metabolism in Dendritic Cells
Authors: Yuan Hong, Indumathi Manoharan, Amol Suryawanshi, Tanmay Majumdar, Melinda L. Angus-Hill, Pandelakis A. Koni, Balaji Manicassamy, Andrew L. Mellor, David H. Munn, Santhakumar Manicassamy
Journal: Cancer Research (2015)

Tumors actively suppress antitumor immunity, creating formidable barriers to successful cancer immunotherapy. The molecular mechanisms underlying tumor-induced immune tolerance are largely unknown. In the present study, we show that dendritic cells (DC) in the tumor microenvironment acquire the ability to metabolize vitamin A to produce retinoic acid (RA), which drives regulatory T-cell responses and immune tolerance. Tolerogenic responses were dependent on induction of vitamin A-metabolizing enzymes via the β-catenin/T-cell factor (TCF) pathway in DCs. Consistent with this observation, DC-specific deletion of β-catenin in mice markedly reduced regulatory T-cell responses and delayed melanoma growth. Pharmacologic inhibition of either vitamin A-metabolizing enzymes or the β-catenin/TCF4 pathway in vivo had similar effects on tumor growth and regulatory T-cell responses. Hence, β-catenin/TCF4 signaling induces local regulatory DC and regulatory T-cell phenotypes via the RA pathway, identifying this pathway as an important target for anticancer immunotherapy.
Preterm birth in twins after subfertility treatment: population based cohort study
Authors: Hans Verstraelen, Sylvie Goetgeluk, Catherine Derom, Stijn Vansteelandt, Robert Derom, Els Goetghebeur, Marleen Temmerman
Journal: BMJ (2005)

To assess gestational length and prevalence of preterm birth among medically and naturally conceived twins; to establish the role of zygosity and chorionicity in assessing gestational length in twins born after subfertility treatment.Population based cohort study.Collaborative network of 19 maternity facilities in East Flanders, Belgium (East Flanders prospective twin survey).4368 twin pairs born between 1976 and 2002, including 2915 spontaneous twin pairs, 710 twin pairs born after ovarian stimulation, and 743 twin pairs born after in vitro fertilisation or intracytoplasmic sperm injection.Gestational length and prevalence of preterm birth.Compared with naturally conceived twins, twins resulting from subfertility treatment had on average a slightly decreased gestational age at birth (mean difference 4.0 days, 95% confidence interval 2.7 to 5.2), corresponding to an odds ratio of 1.6 (1.4 to 1.8) for preterm birth, albeit confined to mild preterm birth (34-36 weeks). The adjusted odds ratios of preterm birth after subfertility treatment were 1.3 (1.1 to 1.5) when controlled for birth year, maternal age, and parity and 1.6 (1.3 to 1.8) with additional control for fetal sex, caesarean section, zygosity, and chorionicity. Although an increased risk of preterm birth was therefore seen among twins resulting from subfertility treatment, the risk was largely caused by a first birth effect among subfertile couples; conversely, the risk of prematurity was substantially levelled off by the protective effect of dizygotic twinning.Twins resulting from subfertility treatment have an increased risk of preterm birth, but the risk is limited to mild preterm birth, primarily by virtue of dizygotic twinning.
STUDIES ON THE TWORT-D'HERELLE PHENOMENON
Authors: C. Ionesco-Mihaiesti
Journal: The Journal of Experimental Medicine (1924)

1. The experiments here reported were carried out with a lytic principle isolated from the feces of normal rabbits. 2. It seems that bacteriophage is constantly present in the feces of caged laboratory rabbits. 3. A lytic filtrate active for Strain Shiga 73 (in a dilution of 1:1,000,000) and for the typhoid bacillus (in a dilution of 1:1,000), after twenty successive passages with Shiga bacillus was active, for its homologous strain, in a dilution of about 1:10,000,000,000 but no longer possessed any lytic activity for the typhoid strain. The same filtrate, after twenty successive passages with typhoid bacillus, was similarly active in a dilution of 1:10,000,000,000 for the typhoid strain but was only feebly active for the Shiga strain. 4. The passage of the lytic principle through collodion membranes was never observed. 5. No appreciable diminution in the activity of the filtrates was observed after exposure to cholesterol or lecithin. Killed bacterial suspensions, however, were found to exert a considerable neutralizing effect on the active principle. 6. Formol titrations of lysed cultures lead to the conclusion that the bacteriolysis caused by the bacteriophage is not a true proteolysis but rather a simple plasmolysis of the bacterial cell and not a splitting effect of the protein molecule. 7. We have never obtained active filtrates with the leucocytes of immune animals by the method of Lisbonne, Boulet, and Carrère (14). 8. It would appear, from the experiments, that the immunization of rabbits with the lytic principle results in the disappearance of the bacteriophage from their intestines. 9. All the sera from rabbits immunized with antityphoid or antiShiga filtrates agglutinated respectively the typhoid or Shiga bacilli. 10. Similarly, these sera fixed complement strongly in the presence of the homologous antigen. Five or six times the amount of serum was required to fix complement in the presence of heterologous antigen. 11. All of the immune sera were found to be more or less antilytic. In no case was a strictly specific antilysin obtained.
Androgen receptor gene and male infertility
Authors: E L Yong, C J Loy, K S Sim
Journal: Human Reproduction Update (2003)

Androgens are critical steroid hormones that determine the expression of the male phenotype. Their actions are mediated by a single androgen receptor (AR) which, upon ligand binding, translocates to the nucleus to regulate the expression of androgen-responsive genes. Mutations that disrupt AR function totally result in the complete feminization of 46 XY individuals and the complete androgen insensitivity syndrome. Studies have revealed that AR mutations that do not lead to complete abrogation of its activity can cause a wide spectrum of milder androgen insensitivity syndromes, from ambiguous genitalia in newborn infants to 'idiopathic' male infertility. Recent studies indicate that missense amino-acid substitutions in the ligand-binding domain of the AR result in infertility through a novel mechanism that involves defective protein–protein interactions between receptor domains and coactivator proteins. Independent of missense mutations, studies involving Singaporean, Australian, North American and Japanese subjects indicate that increases in length of a trinucleotide repeat (CAG) tract, encoding a polyglutamine stretch in the transactivation domain of the AR, are associated with increased risk of defective spermatogenesis and undermasculinization. This association was however not observed in European populations, suggesting that the genetic background may play a significant role in the expression of the AR defects.