tbuckley/cabot-search huggingface dataset:
Genetics of Native Airway Responsiveness in Mice
Authors: GEORGE T. De SANCTIS, JEFFREY M. DRAZEN
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The inbred mouse represents a powerful tool for dissecting both simple and complex traits. Genetic studies in the mouse should identify disease genes acting in the same biochemical pathway as in the human. Problems associated with genetic heterogeneity, inability to control environmental conditions, lack of an abundant supply of genetic markers, and ethical considerations regarding human genetic crosses are but some of the reasons to study airway responsiveness in the mouse. At present, only a handful of studies have shed light on the genetics of airway responsiveness; even fewer have sought to identify genetic loci that regulate this trait. It is clear that both genetic and environmental factors influence the asthma phenotype and that genetic background is an important consideration when interpreting segregation analysis data. The controversy over the specific mode of inheritance and number and location of quantitative trait loci (QTL) illustrates the need for additional studies. However, given that numerous candidate loci implicated in the pathogenesis of asthma map near QTLs identified in two recent studies, and given the considerable homology between the human and mouse genome, a targeted search for susceptibility genes is warranted in the human. Ideally, these regions will demonstrate linkage in humans. Thus, further work remains to be done to create detailed maps of the regions of linkage in the mouse, and to ultimately identify gene(s) that modify airway responsiveness. mice.
Intratumoral Cytokines and Tumor Cell Biology Determine Spontaneous Breast Cancer–Specific Immune Responses and Their Correlation to Prognosis
Authors: Christoph Domschke, Florian Schuetz, Yingzi Ge, Tobias Seibel, Christine Falk, Benedikt Brors, Israel Vlodavsky, Nora Sommerfeldt, Hans-Peter Sinn, Marie-Christine Kühnle, Andreas Schneeweiss, Alexander Scharf, Christof Sohn, Volker Schirrmacher, Gerhard Moldenhauer, Frank Momburg, Philipp Beckhove
Journal: Cancer Research (2009)

Spontaneous immune responses in cancer patients have been described. Yet their clinical relevance and the conditions for their generation remain unclear. We characterized conditions that determine immune responses in primary breast cancer patients. We used tetramer analysis, ex vivo IFN-gamma ELISPOT, cytotoxicity assays, and ELISA in 207 untreated patients and 12 Her-2/neu-specific CD8 T-cell lines to evaluate tumor-specific T cells (TC) in the bone marrow or MUC1-specific antibodies in the blood. Multiplex analysis was performed to quantify 27 intratumoral cytokines, chemokines, and growth factors. Results were compared with multiple pathologic and clinical parameters of the patients and tumors. Forty percent of the patients showed tumor-specific TC responses. These correlated with tumors of high differentiation, estrogen receptor expression, and low proliferative activity, and with a reduced cancer mortality risk. High tumor cell differentiation correlated with increased intratumoral, but not plasma, concentrations of IFN-alpha and reduced transforming growth factor (TGF)beta1. In an in vitro priming experiment these two cytokines increased or inhibited, respectively, the capacity of dendritic cells to induce tumor-reactive TC. Tumor-specific B-cell responses, mainly of IgM isotype, were detectable in 50% of the patients and correlated with advanced tumor stage, increased TGFbeta1, reduced IFN-alpha, and absence of TC responses. We show here that different types of immune responses are linked to distinct cytokine microenvironments and correlate with prognosis-relevant differences in tumor pathobiology. These findings shed light on the relation between immune response and cancer prognosis.
Effect of cholecystectomy on bowel function: a prospective, controlled study
Authors: S D Hearing, L A Thomas, K W Heaton, L Hunt
Journal: Gut (1999)

<h3>BACKGROUND</h3> Published estimates of the prevalence of postcholecystectomy diarrhoea derive from retrospective or uncontrolled data. They ignore functional bowel syndromes and possible changes in diet and drug use. <h3>AIMS</h3> To determine prospectively whether and how often cholecystectomy leads to changes in bowel function and bowel symptoms, especially to liquid stools, over and above any non-specific effect of laparoscopic surgery. <h3>SUBJECTS</h3> Patients: 106 adults undergoing laparoscopic cholecystectomy (85 women, 21 men). Controls: 37 women undergoing laparoscopic sterilisation. <h3>METHODS</h3> Before and 2–6 months after surgery patients were administered questionnaires about bowel frequency, bowel symptoms, diet, and drugs, and kept records of five consecutive defecations with assessment of stool form or appearance on a seven point scale. <h3>RESULTS</h3> In cholecystectomised women, stated bowel frequency increased, on average by one movement a week, and fewer subjects felt that they became constipated. However, records showed no consistent change in bowel frequency, stool form, or defecatory symptoms. Six women reported diarrhoea after the operation but in only one was it clearly new and in her it was mild. Change in dietary fibre intake did not associate with change in bowel function but stopping constipating drugs did in a minority. In women being sterilised there was no consistent change in bowel function. In men having cholecystectomy no consistent changes were observed. <h3>CONCLUSIONS</h3> In women, cholecystectomy leads to the perception of less constipation and slightly more frequent defecations but short term recordings show no consistent change in bowel function. Clinical diarrhoea develops rarely and is not severe.
Effect of norepinephrine and cyclic AMP on intracellular sodium ion activity and contractile force in canine cardiac Purkinje fibers.
Authors: M S Pecker, W B Im, J K Sonn, C O Lee
Journal: Circulation Research (1986)

The effect of norepinephrine on the Na+-K+ pump was investigated by simultaneously measuring intracellular sodium ion activity (aiNa) and contractile force of canine cardiac Purkinje fibers driven at 1.0 Hz in K+-free solution, high K+ solution, and in the presence of tetrodotoxin. In Tyrode solution containing 5.4mM [K+]o, 10(-6) M norepinephrine decreased aiNa, whereas in K+-free solution 10(-6) M norepinephrine did not lower aiNa. 16.2 mM [K+]o decreased aiNa from 8.8 +/- 0.9 mM to 6.5 +/- 0.5 mM (mean +/- SD, n = 5). Exposure to 10(-6) M norepinephrine in the presence of high [K+]o further decreased aiNa by 0.7 +/- 0.4 mM. This further decrease was prevented by exposure to 2.5 X 10(-6) M strophanthidin (n = 4). Blockade of the fast sodium channel with 5 X 10(-6) M tetrodotoxin lowered aiNa from 8.5 +/- 1.3 mM to 7.4 +/- 1.1 mM (n = 4). Exposure to 10(-6) M norepinephrine in the presence of tetrodotoxin further lowered aiNa by 0.9 +/- 0.2 mM. We also studied the effects of the analogues of adenosine 3':5'-cyclic monophosphate, N6, 2'-0-dibutyryladenosine 3':5'-cyclic monophosphate, and 8-(4-chlorophenylthiol)-adenosine 3':5'-cyclic monophosphate on aiNa and twitch tension. Both analogues lowered to aiNa and increased twitch tension mimicking the effects of norepinephrine. Our results support the hypothesis that norepinephrine lowers aiNa by stimulating the Na+-K+ pump in this tissue. This stimulation appears to be mediated by adenosine 3':5'-cyclic monophosphate and does not appear to be due to intercellular K+ accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Origin and use of embryonic and adult stem cells in differentiation and tissue repair
Authors: R Passier
Journal: Cardiovascular Research (2003)

Stem cells are self-renewing, unspecialised cells that can give rise to multiple cell types of all tissues of the body. They can be derived from the embryo, foetus and adult. The ability of stem cells to divide but also to differentiate to specialised cell types like nerve and muscle, have made them candidates on which to base therapies for diseases and disorders for which no, or only partially effective, therapies are available. Replacement of defective or absent cells in defective tissues and organs could represent a cure. Here, we introduce the background to stem cell research and review the present state-of-the-art in stem cell biology, directed differentiation and tissue repair. In particular, we distinguish embryonic versus adult sources of stem cells and data derived from animal versus human experiments in order to place current research and perspectives for clinical application in their correct context.
An Essential Role for Nuclear Factor κB in Promoting Double Positive Thymocyte Apoptosis
Authors: Thore Hettmann, Joseph DiDonato, Michael Karin, Jeffrey M. Leiden
Journal: The Journal of Experimental Medicine (1999)

To examine the role of nuclear factor (NF)-κB in T cell development and activation in vivo, we produced transgenic mice that express a superinhibitory mutant form of inhibitor κB-α (IκB-αA32/36) under the control of the T cell–specific CD2 promoter and enhancer (mutant [m]IκB-α mice). Thymocyte development proceeded normally in the mIκB-α mice. However, the numbers of peripheral CD8+ T cells were significantly reduced in these animals. The mIκB-α thymocytes displayed a marked proliferative defect and significant reductions in interleukin (IL)-2, IL-3, and granulocyte/macrophage colony-stimulating factor production after cross-linking of the T cell antigen receptor. Perhaps more unexpectedly, double positive (CD4+CD8+; DP) thymocytes from the mIκB-α mice were resistant to α-CD3–mediated apoptosis in vivo. In contrast, they remained sensitive to apoptosis induced by γ-irradiation. Apoptosis of wild-type DP thymocytes after in vivo administration of α-CD3 mAb was preceded by a significant reduction in the level of expression of the antiapoptotic gene, bcl-xL. In contrast, the DP mIκB-α thymocytes maintained high level expression of bcl-xL after α-CD3 treatment. Taken together, these results demonstrated important roles for NF-κB in both inducible cytokine expression and T cell proliferation after TCR engagement. In addition, NF-κB is required for the α-CD3–mediated apoptosis of DP thymocytes through a pathway that involves the regulation of the antiapoptotic gene, bcl-xL.
(22) Juvenile pemphigoid
Authors: A. Cattell, E. Waddington
Journal: British Journal of Dermatology (1973)

Journal Article (22) Juvenile pemphigoid Get access A. Cattell, A. Cattell Department of Dermatology, University Hospital of Wales, Cardiff Search for other works by this author on: Oxford Academic Google Scholar E. Waddington E. Waddington Department of Dermatology, University Hospital of Wales, Cardiff Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 89, Issue s9, 1 July 1973, Pages 88–91, https://doi.org/10.1111/j.1365-2133.1973.tb03455.x Published: 01 July 1973
Neural stem cell transplantation can ameliorate the phenotype of a mouse model of spinal muscular atrophy
Authors: Stefania Corti, Monica Nizzardo, Martina Nardini, Chiara Donadoni, Sabrina Salani, Dario Ronchi, Francesca Saladino, Andreina Bordoni, Francesco Fortunato, Roberto Del Bo, Dimitra Papadimitriou, Federica Locatelli, Giorgia Menozzi, Sandra Strazzer, Nereo Bresolin, Giacomo P. Comi
Journal: Journal of Clinical Investigation (2008)

Spinal muscular atrophy (SMA), a motor neuron disease (MND) and one of the most common genetic causes of infant mortality, currently has no cure. Patients with SMA exhibit muscle weakness and hypotonia. Stem cell transplantation is a potential therapeutic strategy for SMA and other MNDs. In this study, we isolated spinal cord neural stem cells (NSCs) from mice expressing green fluorescent protein only in motor neurons and assessed their therapeutic effects on the phenotype of SMA mice. Intrathecally grafted NSCs migrated into the parenchyma and generated a small proportion of motor neurons. Treated SMA mice exhibited improved neuromuscular function, increased life span, and improved motor unit pathology. Global gene expression analysis of laser-capture-microdissected motor neurons from treated mice showed that the major effect of NSC transplantation was modification of the SMA phenotype toward the wild-type pattern, including changes in RNA metabolism proteins, cell cycle proteins, and actin-binding proteins. NSC transplantation positively affected the SMA disease phenotype, indicating that transplantation of NSCs may be a possible treatment for SMA.
Physicians and Patient Spirituality
Authors: John Graner
Journal: Annals of Internal Medicine (2000)

Letters7 November 2000Physicians and Patient SpiritualityJohn Graner, MDJohn Graner, MDMayo Clinic; Rochester, MN 55906 (Graner)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-133-9-200011070-00028 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Post and colleagues' assertion (1) that "the health care market presses providers in a more holistic direction … that includes attentiveness to patient spirituality," has an oxymoronic flavor to it, worthy of a comment from William Osler's alter ego, Egerton Yorrick Davis (2). The danger here, of course, is the bringing of any aspect of religion into the "marketplace." Because of this danger, we must be ever-diligent to prevent a misguided religiosity in the clinic or hospital. I have seen religious icons hanging in individual physicians' offices, perhaps in an attempt to announce to their patients that ...References1. Post SG, Puchalski CM, Larson DB. Physicians and patient spirituality: professional boundaries, competency, and ethics. Ann Intern Med. 2000;132:578-83. LinkGoogle Scholar2. Tigertt WD. An annotated life of Egerton Yorrick Davis, M.D., an intimate of Sir William Osler. J Hist Med Allied Sci. 1983;38:259-97. CrossrefMedlineGoogle Scholar3. Copp J. Faith and medicine: a growing practice. St Anthony Messenger. 2000;107:23-6. Google Scholar Author, Article, and Disclosure InformationAuthors: John Graner, MDAffiliations: Mayo Clinic; Rochester, MN 55906 (Graner) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoPhysicians and Patient Spirituality: Professional Boundaries, Competency, and Ethics Stephen G. Post , Christina M. Puchalski , and David B. Larson Physicians and Patient Spirituality Christina M. Puchalski , David B. Larson , and Stephen G. Post Physicians and Patient Spirituality Gerald P. Bodey Physicians and Patient Spirituality John Graner Physicians and Patient Spirituality Fritz Baumgartner Metrics Cited bySpiritual, Religious, and Existential Aspects of Palliative CareGrounding Research and Medical Education About Religion in Actual Physician-Patient Interaction: Church Attendance, Social Support, and Older AdultsPhysicians and Patient SpiritualityFritz Baumgartner, MDReligion, Spirituality, and Existentialism Near the End of LifePatient perspectives on spirituality and the patient-physician relationshipPhysicians and Patient SpiritualityGerald P. Bodey, MD 7 November 2000Volume 133, Issue 9Page: 748KeywordsHealth care providersHealth care sectorHospitals ePublished: 7 November 2000 Issue Published: 7 November 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Experience with alemtuzumab plus rituximab in patients with relapsed and refractory lymphoid malignancies
Authors: Stefan Faderl, Deborah A. Thomas, Susan O'Brien, Guillermo Garcia-Manero, Hagop M. Kantarjian, Francis J. Giles, Charles Koller, Alessandra Ferrajoli, Srdan Verstovsek, Barbara Pro, Michael Andreeff, Miloslav Beran, Jorge Cortes, William Wierda, Ngoc Tran, Michael J. Keating
Journal: Blood (2003)
Re: Trends in U.S. Pleural Mesothelioma Incidence Rates Following Simian Virus 40 Contamination of Early Poliovirus Vaccines
Authors: R. A. Vilchez, J. S. Butel
Journal: JNCI Journal of the National Cancer Institute (2003)

We read with interest the recent article in the Journal by Strickler et al. (1), in which the authors performed a retrospective age–period–cohort analysis to estimate the incidence of pleural mesothelioma in individuals potentially exposed to simian virus 40 (SV40) -contaminated poliovirus vaccines. The authors concluded that “Age-specific trends in U.S. pleural mesothelioma incidence rates are not consistent with an effect of exposure to SV40-contaminated poliovirus vaccine” and suggested that “monitoring of vaccine-exposed cohorts should continue.” We wish to raise two issues about this and similar studies (2–4) that address “exposure” to SV40contaminated polio vaccines and the incidence of human cancers. First, although a cohort study is recognized as the best design to identify incidence and natural history of disease (with a known exposure) and may be used to assess multiple outcomes after a single exposure (5), the prevalence of SV40 infections in the human population is not known, and the available data about prevalence are limited and inconclusive (2–4). Second, an important confounding factor in the epidemiologic assessment of malignant mesothelioma is that the actual number of people infected with SV40 through the use of contaminated polio vaccines is not known and may be less than the “exposed” population size assumed in the study by Strickler et al. (1). For example, in the United States, not all vaccine lots were contaminated with SV40, formalin inactivation was expected to reduce the titer of live SV40 in the lots that were contaminated, and successful infection rates by live SV40 are unknown (2–4). Therefore, an inability to identify the population that was actually infected with SV40 through the use of contaminated polio vaccines precludes a meaningful calculation of cancer incidence in relation to exposure to those vaccines. Furthermore, the Institute of Medicine (IOM) Immunization Safety Review Committee found that epidemiologic studies of cancer rates in people potentially “exposed” to SV40-contaminated vaccines, such as the analysis by Strickler et al. (1), are inadequate to evaluate a causal relationship between exposure and disease (2). These limitations led the IOM to “not recommend additional epidemiological studies of people potentially exposed to contaminated polio vaccine” (2). However, the IOM concluded that “the biological evidence is strong that SV40 is a transforming virus” and that “the biological evidence is of moderate strength that SV40 exposure could lead to cancer in humans under natural conditions” (2). Future studies are needed to determine the prevalence of SV40 infections in different human populations. The IOM recognized that gaps in our understanding of the pathogenesis of SV40 in humans are important and recommended “targeted biological research,” including “further study of the transmissibility of SV40 in humans” (2).
Omeprazole enhances efficacy of triple therapy in eradicating Helicobacter pylori.
Authors: T J Borody, P Andrews, G Fracchia, S Brandl, N P Shortis, H Bae
Journal: Gut (1995)

Triple therapy has been recommended as the most effective treatment for Helicobacter pylori eradication. Despite achieving a comparatively high eradication result, however, around 10% of patients still fail to be cured. Omeprazole can enhance efficacy of single and double antibiotic protocols and is particularly effective when combined with clarithromycin and a nitroimidazole. This study examined the effect of combining triple therapy with omeprazole. A prospective, randomised, unblinded, single centre trial was carried out on consecutive patients with symptoms of dyspepsia and H pylori infection confirmed by rapid urease test, microbiological culture, and histological assessment. Patients were given a five times/day, 12 day course of colloidal bismuth subcitrate chewable tablets (108 mg), tetracycline HCl (250 mg), and metronidazole (200 mg) with either 20 mg omeprazole twice daily (triple therapy+omeprazole) or 40 mg famotidine (triple therapy+famotidine) at night. Compliance and side effects were determined using a standard questionnaire form. One hundred and twenty five of 165 triple therapy+omeprazole patients and 124 of 171 triple therapy+famotidine patients returned for rebiopsy four weeks after completion of treatment. Significantly more triple therapy+omeprazole patients achieved eradication 122 of 125 (97.6%) as assessed by negative urease test, culture, and histological assessment, when compared with 110 of 124 (89%) triple therapy+famotidine patients (p = 0.006; chi 2). There were 30 triple therapy+omeprazole (24%) and 26 triple therapy+famotidine (21%) patients with de novo metronidazole resistant H pylori included in the study. Side effects were mild and infrequent and were comparable in both groups, although pain in duodenal ulcer, gastric ulcer, and oesophagitis patients seemed to subside earlier in those taking omeprazole. Compliance (&gt;95% of drugs taken) was achieved by 98% of patients of both groups. A 12 days regimen of triple therapy with omeprazole is more effective in achieving H pylori eradication than is triple therapy plus famotidine. Use of 20 mg omeprazole twice daily rather than 40 mg famotidine with a 12 day, low dose triple therapy enhances eradication to over 97% whether the H pylori is metronidazole sensitive or resistant.
Molecular Characteristics of Malignant Ovarian Germ Cell Tumors and Comparison With Testicular Counterparts: Implications for Pathogenesis
Authors: Sigrid Marie Kraggerud, Christina E. Hoei-Hansen, Sharmini Alagaratnam, Rolf I. Skotheim, Vera M. Abeler, Ewa Rajpert-De Meyts, Ragnhild A. Lothe
Journal: Endocrine Reviews (2013)

This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome profiles of mRNA and microRNA (miRNA), and biomarkers (DNA methylation, gene mutation, individual protein expression) for each mOGCT histological subtype. Parallels between the origin of mOGCT and their male counterpart testicular GCT (TGCT) are discussed from the perspective of germ cell development, endocrinological influences, and pathogenesis, as is the GCT origin in patients with disorders of sex development. Integrated molecular profiles of the 3 main histological subtypes, dysgerminoma (DG), yolk sac tumor (YST), and immature teratoma (IT), are presented. DGs show genomic aberrations comparable to TGCT. In contrast, the genome profiles of YST and IT are different both from each other and from DG/TGCT. Differences between DG and YST are underlined by their miRNA/mRNA expression patterns, suggesting preferential involvement of the WNT/β-catenin and TGF-β/bone morphogenetic protein signaling pathways among YSTs. Characteristic protein expression patterns are observed in DG, YST and IT. We propose that mOGCT develop through different developmental pathways, including one that is likely shared with TGCT and involves insufficient sexual differentiation of the germ cell niche. The molecular features of the mOGCTs underline their similarity to pluripotent precursor cells (primordial germ cells, PGCs) and other stem cells. This similarity combined with the process of ovary development, explain why mOGCTs present so early in life, and with greater histological complexity, than most somatic solid tumors.