tbuckley/cabot-search huggingface dataset:
Human transforming growth factor alpha (TGF-alpha) is digested to a smaller (1-43), less biologically active, form in acidic gastric juice
Authors: T Marchbank
Journal: Gut (2002)

Transforming growth factor alpha (TGF-alpha) is a 50 amino acid peptide with potent proliferative and cytoprotective activity present in gastric mucosa and juice.To determine the forms and biological activity of natural and recombinant TGF-alpha following incubation with acid pepsin.Human gastric juice was obtained under basal conditions from patients taking acid suppressants and from volunteers undergoing intragastric neutralisation.Samples were analysed using mass spectroscopy and/or high pressure liquid chromatography with radioimmunoassay. Biological activity was determined using thymidine incorporation into rat hepatocytes and an indomethacin/restraint induced gastric damage rat model.TGF-alpha(1-50) is cleaved to TGF-alpha(1-43) by acid pepsin and this is the predominant form in normal gastric juice. However, intragastric neutralisation or taking acid suppressants caused the predominant form to be TGF-alpha(1-50). TGF-alpha(1-43) had only half of the ability to maximally stimulate [(3)H]thymidine incorporation into primary rat hepatocytes (28 177 (1130) DPM/well for 2.16 nM TGF-alpha(1-43) v 63 184 (3536) DPM/well for TGF-alpha(1-50); p<0.001). A similar reduced potency was seen when used in an indomethacin induced rat gastric damage model (0.18 micro mol/kg/h of TGF-alpha(1-43) reduced ulcer area by 19% whereas TGF-alpha(1-50) reduced area by 62%; p<0.001).TGF-alpha(1-50) is cleaved to the TGF-alpha(1-43) form by acid pepsin, causing 2-5-fold loss of biological activity. Such changes may have relevance to the actions of acid suppressants and the importance of this peptide in both normal and abnormal growth.
Cytokine transcriptional events during helper T cell subset differentiation.
Authors: J A Lederer, V L Perez, L DesRoches, S M Kim, A K Abbas, A H Lichtman
Journal: The Journal of Experimental Medicine (1996)

The molecular basis for changes in cytokine expression during T helper (Th) cell subset differentiation is not well understood. We have characterized transcriptional events related to cytokine gene expression in populations of naive T cell receptor-transgenic T cells as they are driven in vitro toward Th1 or Th2 phenotypes by interleukin (IL)-12 or IL-4 treatment, respectively. Quantitative reverse transcriptase-polymerase chain reaction analysis of cytokine transcripts indicates that interferon (IFN) gamma, IL-4, and IL-2 mRNA are expressed with distinct kinetics after naive T cells are stimulated with antigen and either IL-4 or IL-12. IFN-gamma mRNA appears as early as 6 h in IL-12-treated cultures, IL-4 appears only after 48 h in IL-4-treated cultures, and IL-2 is equivalently expressed in both types of cultures. Analyses were performed to determine if there were any differences in activation of IL-2 or IL-4 transcription factors that accompanied Th1 versus Th2 differentiation. These studies demonstrated that signal transducer and activator of transcription 6 (STAT6) binds to a sequence in the IL-4 promoter and that this STAT6-binding site can support IL-4-dependent transcription of a linked heterologous promoter. Prolonged activation of STAT6 is characteristic of populations undergoing Th2 differentiation. Furthermore, STAT6 is activated in an autocrine manner when differentiated Th2 populations are stimulated by antigen receptor ligation. Th1 populations derived from IL-12 plus antigen treatment of naive T cells remain responsive to IL-4 as indicated by induction of STAT6 and IL-4 mRNA. These data indicate that Th1 and Th2 differentiation represents the combination of different, apparently independently regulated transcriptional events. Furthermore, among transcription factors that bind to the IL-4 or IL-2 promoters, STAT6 is the one whose activation distinguishes Th2 versus Th1 development.
Metformin for Obesity in Children and Adolescents: A Systematic Review
Authors: Min Hae Park, Sanjay Kinra, Kirsten J. Ward, Billy White, Russell M. Viner
Journal: Diabetes Care (2009)

To summarize the efficacy of metformin in reducing BMI and cardiometabolic risk in obese children and adolescents without diabetes.We performed a systematic review and meta-analysis of randomized controlled trials (RCTs). Double-blind RCTs of > or =6 months duration in obese subjects age < or =19 years without diabetes were included. Our primary outcomes of interest include changes in BMI and measures of insulin sensitivity.Five trials met inclusion criteria (n = 320 individuals). Compared with placebo, metformin reduced BMI by 1.42 kg/m(2) (95% CI 0.83-2.02) and homeostasis model assessment insulin of resistance (HOMA-IR) score by 2.01 (95% CI 0.75-3.26).Metformin appears to be moderately efficacious in reducing BMI and insulin resistance in hyperinsulinemic obese children and adolescents in the short term. Larger, longer-term studies in different populations are needed to establish its role in the treatment of overweight children.
Ten-Year Survival in Patients With <i>BRCA1</i>-Negative and <i>BRCA1</i>-Positive Breast Cancer
Authors: Tomasz Huzarski, Tomasz Byrski, Jacek Gronwald, Bohdan Górski, Pawel Domagała, Cezary Cybulski, Oleg Oszurek, Marek Szwiec, Karol Gugała, Malgorzata Stawicka, Zbigniew Morawiec, Tomasz Mierzwa, Hanna Janiszewska, Ewa Kilar, Elzbieta Marczyk, Beata Kozak-Klonowska, Monika Siołek, Dariusz Surdyka, Rafal Wiśniowski, Michal Posmyk, Ping Sun, Jan Lubiński, Steven A. Narod
Journal: Journal of Clinical Oncology (2013)

To estimate 10-year overall survival (OS) rates for patients with early-onset breast cancer, with and without a BRCA1 mutation, and to identify prognostic factors among those with BRCA1-positive breast cancer.A total of 3,345 women with stage I to III breast cancer, age ≤ 50 years, were tested for three founder mutations in BRCA1. Information on tumor characteristics and treatments received was retrieved from medical records. Dates of death were obtained from the vital statistics registry. Survival curves for the mutation-positive and -negative subcohorts were compared. Predictors of OS were determined using the Cox proportional hazards model.Of the 3,345 patients enrolled onto the study, 233 (7.0%) carried a BRCA1 mutation. The 10-year survival rate for mutation carriers was 80.9% (95% CI, 75.4% to 86.4%); for noncarriers, it was 82.2% (95% CI, 80.5% to 83.7%). The adjusted hazard ratio (HR) associated with carrying a BRCA1 mutation was 1.81 (95% CI, 1.26 to 2.61). Among BRCA1 carriers with a small (< 2 cm) node-negative tumor, the 10-year survival rate was 89.9%. Among BRCA1 mutation carriers, positive lymph node status was a strong predictor of mortality (adjusted HR, 4.1; 95% CI, 1.8 to 8.9). Oophorectomy was associated with improved survival in BRCA1 carriers (adjusted HR, 0.30; 95% CI, 0.12 to 0.75).The 10-year survival rate among women with breast cancer and a BRCA1 mutation is similar to that of patients without a BRCA1 mutation. Among women with a BRCA1 mutation, survival was much improved after oophorectomy.
Prevalence of Chlamydia trachomatis infection in women having cervical smear tests.
Authors: J. R. Smith, J. Murdoch, D. Carrington, C. E. Frew, A. J. Dougall, H. MacKinnon, D. Baillie, D. M. Byford, C. A. Forrest, J. A. Davis
Journal: BMJ (1991)

OBJECTIVE--To determine the prevalence of sexually transmitted diseases in patients with normal and abnormal cervical smears. DESIGN--A prospective study of asymptomatic women with normal cervical smears attending their general practitioner and newly referred patients with abnormal smears attending a colposcopy clinic. SETTING--A hospital based colposcopy clinic and an urban general practice (list size 5500) in north west Glasgow. SUBJECTS--197 asymptomatic women attending their general practitioner for cervical smear tests and 101 randomly selected patients attending the colposcopy clinic for investigation of abnormal smears. MAIN OUTCOME MEASURES--Presence of various sexually transmitted infections as determined by culture and serological tests. RESULTS--Of the 101 women with cytological abnormalities, six had current chlamydial infection proved by culture and none had gonococcal infection; of the 197 women with normal smears, 24 (12%) had a chlamydial infection and two had gonorrhoea. Serological studies for Chlamydia trachomatis specific antibody also indicated that a large proportion of patients had been exposed to this agent in both groups. There was no significant difference between the groups in the prevalence of any sexually transmitted disease studied. CONCLUSION--A high prevalence of chlamydial infection is present in women in north west Glasgow irrespective of their cervical cytological state.
A multidimensional approach to the mind-brain: Behaviour versus schemata versus cognition?
Authors: Jonathan K. Foster
Journal: Behavioral and Brain Sciences (2000)

Arbib, Érdi, and Szentágothai's book seeks to present a multidisciplinary, multistrategied approach to the study of the mind-brain, encompassing structural, functional, and dynamic perspectives. However, the articulated framework is somewhat underspecified at the cognitive level. The representational level of analysis will need to be fleshed out if the explanatory potential of Arbib et al.'s framework is to be fulfilled.
Learn from the past and create the future: the 2013 ATS/ERS statement on pulmonary rehabilitation
Authors: Sally J. Singh, Richard L. ZuWallack, Chris Garvey, Martijn A. Spruit
Journal: European Respiratory Journal (2013)

Pulmonary rehabilitation is an established intervention for the management of chronic obstructive pulmonary disease (COPD); indeed, the delivery of rehabilitation has become routine care for individuals with moderate to severe disease [1]. To guide the delivery of pulmonary rehabilitation, practitioners have looked to the European Respiratory Society (ERS) and the American Thoracic Society (ATS) to offer support in terms of describing the evidence for the intervention and to guide best practice [2]. The new ATS/ERS statement on pulmonary rehabilitation aims to harness international scientific expertise and clinical experience to achieve this challenge [3].

Why a new statement? The 2006 statement provided an excellent reference point for pulmonary rehabilitation [2], but over the past few years there have been several significant developments in the field to warrant a reconsideration of the current position. There is also an obligation to the endorsing societies to ensure that these documents are current and reflect best practice. In June 2010, the process of developing a new statement began. There have been significant developments in our understanding of COPD and the systemic manifestations of the disease, the importance of the intervention in other chronic respiratory disease and the timing of the intervention. The document is complemented by the evidence-based guidelines from the American College of Chest Physicians and American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) [4], which formally graded the quality of the scientific evidence, and the AACVPR guidelines for pulmonary rehabilitation programs, which give practical recommendations [5]. By the very nature of a statement, recommendations cannot be made in the 2013 ATS/ERS statement on pulmonary rehabilitation, as these are the preserve of guidelines.

The current ATS/ERS task force was represented by a broad range of professions that are reflected in the interdisciplinary …
New patients' organisations “are being set up to fail,” MPs are told
Authors: Adrian O'Dowd
Journal: BMJ (2007)

The new bodies that will allow the public a say in how the NHS is run are “being set up to fail,” with a lack of resources, the head of the body that oversees patients' forums has said.

The head of the Commission for Patient and Public Involvement in Health told MPs last week that the government's proposed new local involvement networks (LINks) will be fatally underfunded.

The government proposes that LINks will replace the existing patients' forums; but instead of being concerned with a specific NHS body they will each cover a certain geographical area. Moreover, they will cover social as well as …
Regulation of Angiogenic Factors by HDM2 in Renal Cell Carcinoma
Authors: Veronica A. Carroll, Margaret Ashcroft
Journal: Cancer Research (2008)

Abstract The oncogene HDM2 has been implicated in the regulation of the transcription factor, hypoxia inducible factor (HIF). We show in von Hippel-Lindau (VHL)-defective renal carcinoma cells that express constitutively high levels of HIF-1α and HIF-2α that down-regulation of HDM2 by siRNA leads to decreased levels of both HIF-1α and HIF-2α protein levels. However, we show a differential regulation of HDM2 on the HIF angiogenic targets, vascular endothelial growth factor (VEGF), plasminogen activator inhibitor-1 (PAI-1), and endothelin-1 (ET-1): siRNA to HDM2 leads to increased expression of VEGF and PAI-1 proteins but decreased levels of ET-1. We show that HDM2-mediated regulation of these proteins is independent of VHL and p53 but dependent on a novel action of HDM2. Ablation of HDM2 leads to phosphorylation of extracellular-regulated kinase (ERK)1/2 in renal carcinoma cells. We show that regulation of these angiogenic factors is dependent on ERK1/2 phosphorylation, which can be reversed by addition of the MAP/ERK1/2 kinase inhibitors PD98059 and PD184352. This study identifies a novel role for the HDM2 oncoprotein in the regulation of angiogenic factors in renal cell carcinoma. [Cancer Res 2008;68(2):545–52]
Tumorigenic Effect of 1-Hydrazinophthalazine Hydrochloride in Mice
Authors: Bela Toth
Journal: JNCI Journal of the National Cancer Institute (1978)

A solution of 0.125% 1-hydrazinophthalazine hydrochloride, an antihypertensive drug widely used in humans, was given continuously in drinking water for the life-spans of randomly bred Swiss mice. Consumption of the chemical significantly increased the lung tumor incidence from 36 to 60% in females and from 26 to 46% in males, compared to controls. Histopathologically, the tumors were classified as adenomas and adenocarcinomas of the lungs.
Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation
Authors: Mari Dezawa, Hiroshi Kanno, Mikio Hoshino, Hirotomi Cho, Naoya Matsumoto, Yutaka Itokazu, Nobuyoshi Tajima, Hitoshi Yamada, Hajime Sawada, Hiroto Ishikawa, Toshirou Mimura, Masaaki Kitada, Yoshihisa Suzuki, Chizuka Ide
Journal: Journal of Clinical Investigation (2004)

Bone marrow stromal cells (MSCs) have the capability under specific conditions of differentiating into various cell types such as osteocytes, chondrocytes, and adipocytes. Here we demonstrate a highly efficient and specific induction of cells with neuronal characteristics, without glial differentiation, from both rat and human MSCs using gene transfection with Notch intracellular domain (NICD) and subsequent treatment with bFGF, forskolin, and ciliary neurotrophic factor. MSCs expressed markers related to neural stem cells after transfection with NICD, and subsequent trophic factor administration induced neuronal cells. Some of them showed voltage-gated fast sodium and delayed rectifier potassium currents and action potentials compatible with characteristics of functional neurons. Further treatment of the induced neuronal cells with glial cell line-derived neurotrophic factor (GDNF) increased the proportion of tyrosine hydroxylase-positive and dopamine-producing cells. Transplantation of these GDNF-treated cells showed improvement in apomorphine-induced rotational behavior and adjusting step and paw-reaching tests following intrastriatal implantation in a 6-hydroxy dopamine rat model of Parkinson disease. This study shows that a population of neuronal cells can be specifically generated from MSCs and that induced cells may allow for a neuroreconstructive approach.
Trends in the epidemiology and prescribing of medication for eczema in England
Authors: Colin R Simpson, John Newton, Julia Hippisley-Cox, Aziz Sheikh
Journal: Journal of the Royal Society of Medicine (2009)

Summary Background The prevalence of eczema, particularly in younger children, increased substantially over the second half of the 20th century. Analysis of primary healthcare data-sets offers the possibility to advance understanding about the changing epidemiology of eczema. Aim To investigate recent trends in the recorded incidence, lifetime prevalence, prescribing and consulting behaviour of patients with eczema in England. Methods QRESEARCH is one of the world’s largest national aggregated health databases containing the records of over nine million patients. We extracted data on all patients with a recorded diagnosis of eczema and calculated annual age–sex standardized incidence and lifetime period prevalence rates for each year from 2001–2005. We also analysed the consulting behaviour of these patients when compared with the rest of the QRESEARCH database population. The number of eczema prescriptions issued to people in England was also estimated. Results The age–sex standardized incidence of eczema was 9.58 per 1000 person-years in 2001 and increased to 13.58 per 1000 patients in 2005 (p&lt;0.001). By 2005, eczema affected an estimated 5,773,700 (95% confidence intervals [CI] 5,754,100–5,793,400) individuals in England, who, on average, consulted a general practitioner 4.02 (95% CI 4.01–4.03) times a year. During the study period, the number of eczema related prescriptions increased by 56.6% (95% CI 56.6–56.7), so by 2005 an estimated 13,690,300 (95% CI 13,643,200–13,737,600) prescriptions were issued. Conclusions Recorded incidence and lifetime prevalence of eczema in England continue to increase. Similar increases have also been observed in the estimated number of eczema prescriptions issued to the English population.
Mice Deficient for the Vesicular Acetylcholine Transporter Are Myasthenic and Have Deficits in Object and Social Recognition
Authors: Vania F. Prado, Cristina Martins-Silva, Braulio M. de Castro, Ricardo F. Lima, Daniela M. Barros, Ernani Amaral, Amy J. Ramsey, Tatyana D. Sotnikova, Maria R. Ramirez, Hyung-Gun Kim, Janine I. Rossato, Janaina Koenen, Hui Quan, Vinicius R. Cota, Marcio F.D. Moraes, Marcus V. Gomez, Cristina Guatimosim, William C. Wetsel, Christopher Kushmerick, Grace S. Pereira, Raul R. Gainetdinov, Ivan Izquierdo, Marc G. Caron, Marco A.M. Prado
Journal: Neuron (2006)
Treatment with Ibrutinib Inhibits BTK- and VLA-4–Dependent Adhesion of Chronic Lymphocytic Leukemia Cells <i>In Vivo</i>
Authors: Sarah E.M. Herman, Rashida Z. Mustafa, Jade Jones, Deanna H. Wong, Mohammed Farooqui, Adrian Wiestner
Journal: Clinical Cancer Research (2015)

Ibrutinib leads to a transient lymphocytosis in patients with chronic lymphocytic leukemia (CLL) that develops within hours of starting drug and is due to the efflux of cells from lymphoid tissues into the blood. We therefore sought to investigate the in vivo effect of ibrutinib on migration and adhesion of CLL cells.Patients received single-agent ibrutinib (420 mg daily) on an investigator-initiated phase II trial. Serial blood samples were collected pretreatment and during treatment for ex vivo functional assays.Adhesion of CLL cells to fibronectin was rapidly (within hours) and almost completely inhibited (median reduction 98% on day 28, P < 0.001), while the effect on migration to chemokines was more moderate (median reduction 64%, P = 0.008) and less uniform. Although cell surface expression of key adhesion molecules such as CD49d, CD29, and CD44 were modestly reduced, this was only apparent after weeks of treatment. Stimulation of CLL cells from patients on ibrutinib with PMA, which activates PKC independent of BTK, restored the ability of the cells to adhere to fibronectin in a VLA-4-dependent manner. Finally, the addition of ibrutinib to CLL cells adhered to fibronectin in vitro caused the detachment of 17% of the cells, on average; consisten t with in vivo observations of an increasing lymphocytosis within 4 hours of starting ibrutinib.Inhibition of BTK and VLA-4-dependent adhesion of CLL cells to stroma and stromal components provides a mechanistic explanation for the treatment-induced lymphocytosis and may reduce CD49d-dependent prosurvival signals in the tissue microenvironment.
A Lecture ON SOME PROBLEMS IN CARDIAC PHYSIOLOGY: Delivered before the University of London, June 18th, 1914
Authors: A. F. S. Kent
Journal: BMJ (1914)

BEFO1RE 1892 it was iinpos-iblc to explain thc actioni of the lmammiiiialiani lhcart on the colmparatively simnple liles fotund allequate in the ca'sc of the lheart of tlhe frog, owing to the fact tlhat any miuilscullar coinnexion bctwvcen auricle and venltricle in the llailinalnal Was absolutely denied.Ill 1892 it -was s-hownvl tisat this idea was erroneouts, and that miluscular connexion betwvcen auricle and venitricle did as a fact e-xist.1ii the following years thie details of the conilexioi w oe workedout by variops observers, and the band of tissuie is lnow famiiiliar to eveiry onle as tlle anriculo- veutrictular bulndle.
The Serum and Glucocorticoid-Inducible Kinase SGK1 and the Na+/H+ Exchange Regulating Factor NHERF2 Synergize to Stimulate the Renal Outer Medullary K+ Channel ROMK1
Authors: C. Chris Yun, Monica Palmada, Hamdy M. Embark, Olga Fedorenko, Yuxi Feng, Guido Henke, Iwan Setiawan, Christoph Boehmer, Edward J. Weinman, Sabrina Sandrasagra, Christoph Korbmacher, Philip Cohen, David Pearce, Florian Lang
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Mineralocorticoids stimulate Na+ reabsorption and K+ secretion in principal cells of connecting tubule and collecting duct. The involved ion channels are ENaC and ROMK1, respectively. In Xenopus oocytes, the serum and glucocorticoid-sensitive kinase SGK1 has been shown to increase ENaC activity by enhancing its abundance in the plasma membrane. With the same method, ROMK1 appeared to be insensitive to regulation by SGK1. On the other hand, ROMK1 has been shown to colocalize with NHERF2, a protein mediating targeting and trafficking of transport proteins into the cell membrane. The present study has been performed to test whether NHERF2 is required for regulation of ROMK1 by SGK1. Coexpression of neither NHERF2 nor SGK1 with ROMK1 increases ROMK1 activity. However, coexpression of NHERF2 and SGK1 together with ROMK1 markedly increases K+ channel activity. The combined effect of SGK1 and NHERF2 does not significantly alter the I/V relation of the channel but increases the abundance of the channel in the membrane and decreases the decay of channel activity after inhibition of vesicle insertion with brefeldin. Coexpression of NHERF2 and SGK1 does not modify cytosolic pH but leads to a slight shift of pKa of ROMK1 to more acidic values. In conclusion, NHERF2 and SGK1 interact to enhance ROMK1 activity in large part by enhancing the abundance of channel protein within the cell membrane. This interaction allows the integration of genomic regulation and activation of SGK1 and NHERF2 in the control of ROMK1 activity and renal K+ excretion.
Donor-derived DNA in fingernails among recipients of allogeneic hematopoietic stem-cell transplants
Authors: Daisuke Imanishi, Yasushi Miyazaki, Reishi Yamasaki, Yasushi Sawayama, Jun Taguchi, Hideki Tsushima, Takuya Fukushima, Shinichiro Yoshida, Hiroshi Sasaki, Tomoko Hata, Masao Tomonaga
Journal: Blood (2007)