tbuckley/cabot-search huggingface dataset:
Electrophysiological integration and action potential properties of transplanted cardiomyocytes derived from induced pluripotent stem cells
Authors: Marcel Halbach, Gabriel Peinkofer, Sven Baumgartner, Martina Maass, Mirjam Wiedey, Klaus Neef, Benjamin Krausgrill, Dennis Ladage, Azra Fatima, Tomo Saric, Jürgen Hescheler, Jochen Müller-Ehmsen
Journal: Cardiovascular Research (2013)

AimsInduced pluripotent stem cell-derived cardiomyocytes (iPSCM) are regarded as promising cell type for cardiac cell replacement therapy. We investigated long-term electrophysiological integration and maturation of transplanted iPSCM, which are essential for therapeutic benefit.
Turner’s Syndrome in Adulthood
Authors: M. Elsheikh, D. B. Dunger, G. S. Conway, J. A. H. Wass
Journal: Endocrine Reviews (2002)

Abstract Turner’s syndrome is the most common chromosomal abnormality in females, affecting 1:2,500 live female births. It is a result of absence of an X chromosome or the presence of a structurally abnormal X chromosome. Its most consistent clinical features are short stature and ovarian failure. However, it is becoming increasingly evident that adults with Turner’s syndrome are also susceptible to a range of disorders, including osteoporosis, hypothyroidism, and renal and gastrointestinal disease. Women with Turner’s syndrome have a reduced life expectancy, and recent evidence suggests that this is due to an increased risk of aortic dissection and ischemic heart disease. Up until recently, women with Turner’s syndrome did not have access to focused health care, and thus quality of life was reduced in a significant number of women. All adults with Turner’s syndrome should therefore be followed up by a multidisciplinary team to improve life expectancy and reduce morbidity.
Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study
Authors: Alex Iranzo, Eduard Tolosa, Ellen Gelpi, José Luis Molinuevo, Francesc Valldeoriola, Mónica Serradell, Raquel Sanchez-Valle, Isabel Vilaseca, Francisco Lomeña, Dolores Vilas, Albert LLadó, Carles Gaig, Joan Santamaria
Journal: The Lancet Neurology (2013)
Phase I trial of imatinib in children with newly diagnosed brainstem and recurrent malignant gliomas: A Pediatric Brain Tumor Consortium report1
Authors: Ian F. Pollack, Regina I. Jakacki, Susan M. Blaney, Michael L. Hancock, Mark W. Kieran, Peter Phillips, Larry E. Kun, Henry Friedman, Roger Packer, Anu Banerjee, J. Russell Geyer, Stewart Goldman, Tina Young Poussaint, Matthew J. Krasin, Yanfeng Wang, Michael Hayes, Anthony Murgo, Susan Weiner, James M. Boyett
Journal: Neuro-Oncology (2007)

This study estimated the maximum tolerated dose (MTD) of imatinib with irradiation in children with newly diagnosed brainstem gliomas, and those with recurrent malignant intracranial gliomas, stratified according to use of enzyme-inducing anticonvulsant drugs (EIACDs). In the brainstem glioma stratum, imatinib was initially administered twice daily during irradiation, but because of possible association with intratumoral hemorrhage (ITH) was subsequently started two weeks after irradiation. The protocol was also amended to exclude children with prior hemorrhage. Twenty-four evaluable patients received therapy before the amendment, and three of six with a brainstem tumor experienced dose-limiting toxicity (DLT): one had asymptomatic ITH, one had grade 4 neutropenia and, one had renal insufficiency. None of 18 patients with recurrent glioma experienced DLT. After protocol amendment, 3 of 16 patients with brainstem glioma and 2 of 11 patients with recurrent glioma who were not receiving EIACDs experienced ITH DLTs, with three patients being symptomatic. In addition to the six patients with hemorrhages during the DLT monitoring period, 10 experienced ITH (eight patients were symptomatic) thereafter. The recommended phase II dose for brainstem gliomas was 265 mg/m(2). Three of 27 patients with brainstem gliomas with imaging before and after irradiation, prior to receiving imatinib, had new hemorrhage, excluding their receiving imatinib. The MTD for recurrent high-grade gliomas without EIACDs was 465 mg/m(2), but the MTD was not established with EIACDs, with no DLTs at 800 mg/m(2). In summary, recommended phase II imatinib doses were determined for children with newly diagnosed brainstem glioma and recurrent high-grade glioma who were not receiving EIACDs. Imatinib may increase the risk of ITH, although the incidence of spontaneous hemorrhages in brainstem glioma is sufficiently high that this should be considered in studies of agents in which hemorrhage is a concern.
Engineering Aspects of Hyperthermia Therapy
Authors: Robert B. Roemer
Journal: Annual Review of Biomedical Engineering (1999)

▪ Abstract The continuing accrual of positive results in clinical cancer trials of adjunctive, synergistic hyperthermia therapy remains a strong motivation for the development of improved hyperthermia equipment and software. Indeed, the lack of needed engineering tools can be viewed as the major stumbling block to hyperthermia’s effective clinical implementation. Developing clinically effective systems will be difficult, however, because (a) it requires solving several complex engineering problems, for which (b) setting appropriate design and evaluation goals is currently difficult owing to a lack of critical biological, physiological, and clinical knowledge, two tasks which must (c) be accomplished within a complicated social/political structure.
Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease
Authors: Maria L. Jison, Peter J. Munson, Jennifer J. Barb, Anthony F. Suffredini, Shefali Talwar, Carolea Logun, Nalini Raghavachari, John H. Beigel, James H. Shelhamer, Robert L. Danner, Mark T. Gladwin
Journal: Blood (2004)
Clonal Analysis and Cell Lineages of the Vertebrate Central Nervous System
Authors: M Jacobson
Journal: Annual Review of Neuroscience (1985)

Very little progress in tracing cell lineages in the CNS of vertebrates had been made before the introduction of horseradish peroxidase (HRP) as an intra­ cellular lineage tracer in the frog embryo (Jacobson & Hirose 1978, 1981, Hirose & Jacobson 1979). Conceptual weaknesses and lack of adequate tech­ niques reinforced one another to ensure slow progress (Jacobson 1978, p. 98). Thus, a distinction has traditionally been made between embryos that have  development, in which lineage determines cell fate, and those with regulative development, in which cell interactions determine cell fate, but, in fact, most if not all embryos show a combination of both (Harrison 1933, Weiss 1939, Davidson 1976). I shall propose that there are several lineage modes with different degrees of autonomy. In addition to the determinate lineage mode. which is completely autonomous and in which the relationship between a given progenitor and the phenotype(s) of its descendants is all-or­ none, there are others called indeterminant lineage modes in which the rela­ tionship between ancestral cells and the phenotypes of their descendants is contingent on external conditions to some degree. It is now clear that cell interactions can result in changes in of cellular fates in Uroand Cephalo­ chordates (Tung et a11958, 1960, Nakauchi & Takashita 1983), in which there is rigorous proof that materials localized in the egg and differentially distrib­ uted into different lineages determine the ultimate fates of the differentiated cells (Whittaker 1973, 1979. Jeffery 1983, Jeffery et al 1983). Such unim­ peachable evidence of extensive regulation in mosaic embryos should help to open the minds of those who have been unwilling to admit that determination
Anaphylaxis pathogenesis and treatment
Authors: F. Estelle R. Simons
Journal: Allergy (2011)

To cite this article: Simons FER. Anaphylaxis pathogenesis and treatment. Allergy 2011; 66 (Suppl. 95):31–34. Abstract Anaphylaxis is a serious allergic reaction that is rapid in onset and sometimes leads to death. Understanding mechanisms, triggers, and patient‐specific risk factors for severe or fatal anaphylaxis is critically important. Diagnosis of anaphylaxis is currently based on established clinical criteria. Epinephrine (adrenaline) is the first‐line medication for anaphylaxis treatment and delay in injecting it contributes to biphasic reactions, hypoxic‐ischemic encephalopathy, and fatality. Here, we focus on four important areas of translational research in anaphylaxis: studies of potential new biomarkers to support the clinical diagnosis of anaphylaxis, laboratory tests to distinguish allergen sensitization from clinical risk of anaphylaxis, the primary role of epinephrine (adrenaline) in anaphylaxis treatment, and strengthening the overall evidence base for anaphylaxis treatment.
Prevalence of zoonotic chlamydiae in dairy cattle and contact persons
Authors: Simone Kühlewind, Konrad Sachse, Petra Reinhold, Evelyn Schubert, Juliane Kronsbein, Melanie Ulbrich, Birgit Schärling, Dirk Theegarten, Nadine Matzner, Jürgen Behr, Gerhard Schultze-Werninghaus, Gernot Rohde
Journal: European Respiratory Journal (2011)

Chlamydial infections are a known problem in cattle farming. We want to find out whether they are related to chronic respiratory illness in farmers.  We selected 48 dairy farms with a history or suspicion of chlamydial infections. Nasal and vaginal swabs, milk and fecal samples and paired sera were obtained from 5 cows of each farm. The presence of chlamydiae was analysed by rtPCR, by the ArrayTube DNA microarray test and paired sera were examined using an ELISA. The farmers were clinically examined by lung function testing, serology, allergy skin test, and their induced sputum was rtPCR tested.  The analysis of 48 farms showed that in 31 (64.6%) farms at least 1 sample from at least 1 cow was positive in rtPCR and 12 (25%) farms were positive only by ELISA. Chlamydophila (C.)psittaci and C. pecorum were the most frequently identified species. At one farm, Chlamydia trachomatis was identified in cattle.  So, far 39 individuals have been examined, 12 had respiratory symptoms and 33 were positive in serology. C. pneumoniae IgA occurred in 15 (38.5%) subjects and IgG in 26 (66.7%). Only 2 persons were positive for C. psittaci IgG. In 5 (12.8%) human sputum samples Chlamydia trachomatis was identified.  We found a prevalence of 64.6% (rtPCR), which is a wide dissemination of chlamydial infections in cattle herds. In humans, we found signs of an immune reaction against zoonotic C. psittaci in 2 subjects, which had regular contact to birds. The cattle of these farms were tested negative.  The presence of Chlamydia trachomatis in 5 sputum samples is remarkable and interesting and needs further investigation, as well as the detection of Chlamydia trachomatis of 4 cows. The farmers of this farm have not yet been examined.
Ser-322 Is a Critical Site for PKC Regulation of the MDCKCell Taurine Transporter (pNCT)
Authors: XIAOBIN HAN, ANDREA M. BUDREAU, RUSSELL W. CHESNEY
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Previous studies have shown that the Madin—Darby canine kidney cell taurine transporter (pNCT) is downregulated by protein kinase C (PKC) activation. In this study, it is hypothesized that the highly conserved serine-322 (Ser-322) located in the fourth intracellular segment (S 4 ) may play an important role in the function of taurine transporter, which is modulated by PKC phosphorylation. It is demonstrated that Ser-322 is the critical site of PKC phosphorylation, as determined by site-directed mutagenesis. When Ser-322 of pNCT was changed to alanine (S322A) and this mutant was evaluated in an oocyte expression system, taurine transport activity increased threefold compared with control (wild-type pNCT). Activation of PKC by the active phorbol ester 12-myristate 13-acetate did not influence taurine transport by mutant S322A. Kinetic analysis showed that the mutation of Ser-322 essentially changed the V max , rather than the K m , of the transporter. Mutation of all other PKC consensus sites did not affect transporter activity when expressed in the oocyte system. Western blot analysis showed that expression of taurine transporter protein was similar in oocytes injected with either wild-type or mutant pNCT cRNA, indicating that the enhanced taurine transport activity by mutant S322A was not caused by a greater amount of transporter expressed in the oocyte. Furthermore, this study demonstrated that the taurine transporter was phosphorylated after PKC activation, and this effect was not observed in mutant S322A. In conclusion, Ser-322 is critical in PKC regulation of taurine transporter activity. The steady-state taurine transporter activity is tightly controlled by endogenous PKC phosphorylation of Ser-322, which is located in the fourth intracellular segment of the taurine transporter.
Antihypertensive Medication Prescribing in 27,822 Elderly Canadians With Diabetes Over the Past Decade
Authors: Finlay A. McAlister, Norman R.C. Campbell, Minh Duong-Hua, Zhongliang Chen, Karen Tu
Journal: Diabetes Care (2006)

OBJECTIVE—The purpose of this study was to examine whether prescribing practices for elderly individuals with diabetes and hypertension changed over the past decade. RESEARCH DESIGN AND METHODS—We linked the Ontario Diabetes Database and four administrative databases in Ontario, Canada, to identify 27,822 patients &amp;gt;65 years of age who had diabetes and were newly treated for hypertension between 1 January 1995 and 31 December 2001. All patients were followed for 2 years after their initial antihypertensive medication prescription. RESULTS—The 27,822 patients in this study (mean age 72 years, 51% men) were treated with oral hypoglycemic agents alone (n = 17,128 patients, 62%), insulin alone (n = 2,346, 8%), both oral hypoglycemic agents and insulin (n = 2,205, 8%), or diet alone (n = 6,143, 22%). Management within the first 2 years of hypertension diagnosis consisted of antihypertensive monotherapy in 20,183 patients (73%), two antihypertensive drugs in 6,207 (22%), and three or more drugs in 1,432 (5%); the most frequently chosen antihypertensive drugs were ACE inhibitors (68%), thiazides (15%), and calcium channel blockers (9%). Between 1995 and 2001, physician prescribing practices changed: the population-adjusted rates of antihypertensive drug prescribing increased by 46% (95% CI 33–55%), the proportion of initial antihypertensive prescriptions for ACE inhibitors increased from 54 to 76% (P &amp;lt; 0.0001), and the use of multiple antihypertensive agents within the first 2 years of diagnosis increased from 21 to 32% (P &amp;lt; 0.0001). CONCLUSIONS—Antihypertensive prescribing patterns in elderly individuals with diabetes changed over the past decade in Ontario in directions consistent with the evolving evidence base.
Two distinct antigen-specific suppressor factors induced by the oral administration of antigen.
Authors: J A Mattingly, J M Kaplan, C A Janeway
Journal: The Journal of Experimental Medicine (1980)

The feeding of sheep erythrocytes (SRBC) to mice leads to the production of two distinct T cell-derived suppressor factors by spleen cells. Each has been characterized for specificity, genetic restrictions, and cellular interactions. Fraction I has a 60,000-75,000 mol wt, is specific for antigen, and is suppressive of primary in vitro anti-SRBC responses at all times. It is not restricted by major histocompabitility complex (MHC)- or Igh-linked genes, but it fails to suppress spleen cells derived from any strain of mouse with a B10 background. It acts on an Lyt-2+ T cell to increase suppressive activity. An antiserum has been prepared against this factor that reacts with other, unrelated T cell suppressor factors. Fraction II has an approximately 30,000-40,000 mol wt, is specific for antigen, and has a dual effect on in vitro anti-SRBC responses. On day 3 of culture, it leads to augmentation of the response, whereas at day 5 it suppresses the response. It is not restricted by MHC genes, but it is restricted by Igh-linked genets. It acts by activating an Ly-1 t cell to both help and induce feedback suppression. These factors, and the antisera prepared against them, should allow more precise dissection of the molecular pathways by which immunoregulatory cells communicate with one another.
Controversial issues in early-stage breast cancer: a global collaborative survey, supported by the European Society for Medical Oncology (ESMO)
Authors: D. Zardavas, F. Ades, I.B. Spasojevic, L. Pugliano, M. Capelan, M. Paesmans, E. de Azambuja, M. Piccart
Journal: Annals of Oncology (2014)
P59 Differing patterns of new immigrant GP registration among ethnic subgroups determine the importance of additional strategies for models of new immigrant screening
Authors: R. K. Panchal, P. Haldar, G. Woltmann
Journal: Thorax (2011)

<h3>Introduction</h3> New immigrant GP registration databases maybe an important tool for identifying recent immigrants to the UK at high risk of latent infection with <i>M tuberculosis</i> (LTBI), who may benefit from screening and treatment to prevent tuberculosis (TB). However, effectiveness of this strategy is determined by the proportion of immigrants that register and the time after UK entry that registration occurs. <h3>Aims</h3> To evaluate whether differences exist in the pattern of GP registration onto the new immigrant registration database for Leicestershire (Flag-4), between immigrants stratified by age group (&lt;16, 16–35 or =36 years) and ethnicity (Indian sub-continent [ISC] or Black African). <h3>Methods</h3> A retrospective analysis was performed of all immigrants entering the UK after 1999 that were Flag-4 registered between 2000 and 2010 (N=29186) and collated with data for all TB notifications over the same period (N=884). Comparisons were made between immigrants developing TB and staying healthy; and between TB cases occurring in foreign born persons captured or missed by the new immigrant database. Among captured cases, the proportion with a notification date at least 12 months after UK entry and 4 months after GP registration were considered preventable. <h3>Results</h3> There was a significant and inverse relationship for the proportions of cases captured and missed by the Flag-4 system in black Africans and ISC immigrants (Abstract P59 table 1, p&lt;0.001). The higher proportion of missed cases in black Africans was evident for both adult age groups but not children. Among registered immigrants, those developing TB had a significantly longer delay to registration (mean difference [95% CI] 420 [259 to 580] days, p&lt;0.001). Compared with age stratified ISC immigrants, time to registration was significantly longer for black Africans aged 16–35 years (mean difference 832 days, p&lt;0.001). However, the proportion of preventable cases in registered immigrants was similar between ISC and black Africans (83.3% and 90.2%). <h3>Conclusions</h3> Strategies to encourage early registration by new immigrants with a GP may improve utility of this resource for screening. However, greater emphasis on complementary strategies, including engagement of third sector organisations is needed, particularly for identifying black African immigrants at risk of TB.
Rapp-Hodgkin and Hay-Wells ectodermal dysplasia syndromes represent a variable spectrum of the same genetic disorder
Authors: S.E. Clements, T. Techanukul, S.T. Holden, J.E. Mellerio, H. Dorkins, F. Escande, J.A. McGrath
Journal: British Journal of Dermatology (2010)

Journal Article Rapp–Hodgkin and Hay–Wells ectodermal dysplasia syndromes represent a variable spectrum of the same genetic disorder Get access S.E. Clements, S.E. Clements St John's Institute of Dermatology, King's College London (Guy's Campus), London SE1 9EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar T. Techanukul, T. Techanukul St John's Institute of Dermatology, King's College London (Guy's Campus), London SE1 9EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar S.T. Holden, S.T. Holden Department of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.E. Mellerio, J.E. Mellerio St John's Institute of Dermatology, King's College London (Guy's Campus), London SE1 9EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar H. Dorkins, H. Dorkins North West Thames Regional Genetics Service, Kennedy Galton Centre, Harrow, U.K. Search for other works by this author on: Oxford Academic Google Scholar F. Escande, F. Escande Centre de Biologie‐Pathologie, Département de Biologie Moléculaire, CHRU, Lille, France Search for other works by this author on: Oxford Academic Google Scholar J.A. McGrath J.A. McGrath St John's Institute of Dermatology, King's College London (Guy's Campus), London SE1 9EH, U.K. John A. McGrath. E‐mail: john.mcgrath@kcl.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 3, 1 September 2010, Pages 624–629, https://doi.org/10.1111/j.1365-2133.2010.09859.x Published: 01 September 2010
Occupational Exposure to Dusts, Gases, and Fumes and Incidence of Chronic Obstructive Pulmonary Disease in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults
Authors: Amar J. Mehta, David Miedinger, Dirk Keidel, Robert Bettschart, Andreas Bircher, Pierre-Olivier Bridevaux, Ivan Curjuric, Hans Kromhout, Thierry Rochat, Thomas Rothe, Erich W. Russi, Tamara Schikowski, Christian Schindler, Joel Schwartz, Alexander Turk, Roel Vermeulen, Nicole Probst-Hensch, Nino Künzli
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: There is limited evidence from population-based studies demonstrating incidence of spirometric-defined chronic obstructive pulmonary disease (COPD) in association with occupational exposures.Objectives: We evaluated the association between occupational exposures and incidence of COPD in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA).Measurements and Main Results: Prebronchodilator ratio of forced expiratory volume in 1 second over forced vital capacity (FEV1/FVC) was measured in 4,267 nonasthmatic SAPALDIA participants ages 18–62 at baseline in 1991 and at follow-up in 2001–2003. COPD was defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criterion (FEV1/FVC < 0.70) and Quanjer reference equation (FEV1/FVC < lower limit of normal [LLN]), and categorized by severity (≥80% and <80% predicted FEV1 for stage I and stage II+, respectively). Using a job-exposure matrix, self-reported occupations at baseline were assigned exposures to biological dusts, mineral dusts, gases/fumes, and vapors, gases, dusts, or fumes (VGDF) (high, low, or unexposed as reference). Adjusted incident rate ratios (IRRs) of stage I and stage II+ COPD were estimated in mixed Poisson regression models. Statistically significant (P < 0.05) IRRs of stage II+ GOLD and LLN-COPD, indicating risks between two- and fivefold, were observed for all occupational exposures at high levels. Occupational exposure-associated risk of stage II+ COPD was observed mainly in males and ages ≥40 years, and remained elevated when restricted to nonsmokers.Conclusions: In a Swiss working adult population, occupational exposures to biological dusts, mineral dusts, gases/fumes, and VGDF were associated with incidence of COPD of at least moderate severity.
The Treatment of Borderline Personality Disorder: Implications of Research on Diagnosis, Etiology, and Outcome
Authors: Joel Paris
Journal: Annual Review of Clinical Psychology (2008)

The treatment of patients with borderline personality disorder (BPD) is challenging. Making a diagnosis is necessary to plan therapy. But since we do not know the etiology of BPD, treatment cannot be based on a well-established theory. Outcome research shows that most patients recover with time. A series of clinical trials show that a variety of psychotherapies are effective in BPD and that the effects of medication are unimpressive.