tbuckley/cabot-search huggingface dataset:
Input impedance of the pulmonary arterial system in normal man. Effects of respiration and comparison to systemic impedance.
Authors: J P Murgo, N Westerhof
Journal: Circulation Research (1984)

Input impedance of the pulmonary arterial system was determined in 10 subjects undergoing elective cardiac catheterization. No cardiovascular or pulmonary disease was found in these patients. In five of the subjects, systemic arterial impedance was also obtained, so that both systems could be compared. Pulmonary and systemic peripheral resistances were 79 +/- 9 dynes sec/cm5 (mean +/- SEM) and 1016 +/- 50 dynes sec/cm5, respectively. Characteristic impedance of the pulmonary circulation was lower than the characteristic impedance of the systemic circulation: 20 +/- 1 dynes sec/cm5 vs. 47 +/- 9 dynes sec/cm5, respectively. Pulmonary pressure and flow spectra for both systems are also presented. The amplitudes of the harmonics of pressure and flow are smaller for the pulmonary circulation, which is consistent with the lower pressures and more rounded waveforms of the normal pulmonary circulation. In all 10 subjects, input impedance of the pulmonary system was examined during both the inspiratory and expiratory phases of respiration. There was no difference between inspiration and expiration in either pulmonary vascular resistance (77 +/- 10 dynes sec/cm5 vs. 80 +/- 9 dynes sec/cm5, respectively), characteristic impedance (20 +/- 1 dynes sec/cm5 vs. 20 +/- 1 dynes sec/cm5) or in the overall impedance spectrum. Quiet respiration, thus, has no effect on the pulmonary arterial load, and changes in pressure and flow must result from alterations in right ventricular performance.
Overview of national health research systems in sub-Saharan Africa: results of a questionnaire-based survey
Authors: Peter Ebongue Mbondji, Derege Kebede, Chris Zielinski, Wenceslas Kouvividila, Issa Sanou, Paul-Samson Lusamba-Dikassa
Journal: Journal of the Royal Society of Medicine (2014)

Objective To assess the state of national health research systems of countries in the World Health Organization (WHO) African Region. Design A questionnaire-based survey Methods Structured questionnaires were used to solicit health research systems’ relevant information from key informants in each country. Setting Forty-six Member States of the WHO African Region. Participants Key informants from the ministry of health in each country, with the support of WHO Country Offices. Main outcome measures Presence of national health research policy or strategy, priority setting and ethical review of research. Results Of the 44 responding countries, 39 (89%) reportedly had an official national health policy and 37 (84%) had a strategic health plan. A total of 16 (36%) countries reportedly had a functional national health research governance mechanism, nine of which had clear terms of reference; nine (20%) countries had a functional national health research management forum. Functional ethical review committees were reported in 33 countries (75%). Conclusions National health research systems were weak in the countries assessed. Significantly more resources should be allocated to strengthening these systems.
Diacylglycerol Kinase α Is a Critical Signaling Node and Novel Therapeutic Target in Glioblastoma and Other Cancers
Authors: Charli L. Dominguez, Desiree H. Floyd, Aizhen Xiao, Garrett R. Mullins, Benjamin A. Kefas, Wenjun Xin, Melissa N. Yacur, Roger Abounader, Jae K. Lee, Gabriela Mustata Wilson, Thurl E. Harris, Benjamin W. Purow
Journal: Cancer Discovery (2013)

Abstract Although diacylglycerol kinase α (DGKα) has been linked to several signaling pathways related to cancer cell biology, it has been neglected as a target for cancer therapy. The attenuation of DGKα activity via DGKα-targeting siRNA and small-molecule inhibitors R59022 and R59949 induced caspase-mediated apoptosis in glioblastoma cells and in other cancers, but lacked toxicity in noncancerous cells. We determined that mTOR and hypoxia-inducible factor-1α (HIF-1α) are key targets of DGKα inhibition, in addition to its regulation of other oncogenes. DGKα regulates mTOR transcription via a unique pathway involving cyclic AMP. Finally, we showed the efficacy of DGKα inhibition with short hairpin RNA or a small-molecule agent in glioblastoma and melanoma xenograft treatment models, with growth delay and decreased vascularity. This study establishes DGKα as a central signaling hub and a promising therapeutic target in the treatment of cancer. Significance: DGKα, which converts diacylglycerol to phosphatidic acid, regulates critical oncogenic pathways, notably HIF-1α and mTOR. DGKα knockdown and small-molecule inhibition are selectively toxic to human cancer cells but not normal human cells, and DGKα inhibition slows tumor growth, decreases angiogenesis, and increases mouse survival in xenograft models. Cancer Discov; 3(7); 782–97. ©2013 AACR. See related commentary by Bhat and Aldape, p. 726 This article is highlighted in the In This Issue feature, p. 705
Overcoming ethnic differences in lung function: The size & lung function in children (SLIC) study design
Authors: Sooky Lum, Samatha Sonnappa, Tim Cole, Angie Wade, Jonathan Wells, Jane Kirkby, Rachel Bonner, Janet Stocks
Journal: European Respiratory Journal (2013)

Ethnic minorities comprise 40% of the London population (17% South-Asians; 19%Black AfricanC Black; S.Asian & other/mixed. Assessments in schools were performed in 1600 children aged 5-11years on 2 occasions a year apart and included detailed anthropometry; body composition; spirometry and saliva samples (cotinine & DNA analysis). After adjusting for sex, age& standing height, the extent to which ethnic differences in LF can be minimised by including relevant measures of body physique will be determined.   Results:  To date, we received 54% parental consent for participation with successful spirometry from 1088 (45%boys; 33%White; 31%Black; 21%S.Asian; 15%Other/mixed) healthy children(67% of all assessed, excluding 21% on health grounds; 12% failed spirometry). Follow up studies are in progress.   Summary:  This study will facilitate early diagnosis and treatment of lung disease in all children, irrespective of ethnic background. Repeated measures after 1y will facilitate interpretation of serial changes in children with respiratory disease.  Funded by: Wellcome Trust; Asthma UK.
Letter to the editor regarding the report of Duboc<i>et al</i>: connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel disease
Authors: Mitchell L Jones, Christopher J Martoni, Satya Prakash
Journal: Gut (2012)

We read with interest the informative and required investigation of bile-acid dysmetabolism, dysbiosis and inflammation in inflammatory bowel diseases (IBD) by Duboc et al .1 The paper suggests that a characteristic finding of IBD is reduced faecal secondary bile acids (BA), increased conjugated BA and increased sulphated BA.1 The authors link the luminal dysmetabolism of BA to dysbiosis, and the loss of microbiota deconjugation, transformation and desulphation enzymatic functions.1 The authors report convincing evidence demonstrating that a decrease in bacteria-bearing bile salt hydrolase (BSH) activities may be involved in the increase in conjugated BA remaining in the faeces, and show that germ-free mice have a similar loss of microbiota enzymatic function and display similar faecal BA irregularities.1 In addition to their role in dietary lipid absorption, BA are signalling modules activating nuclear receptors, including the farnesoid-X-receptor, the constitutive androstane receptor, the pregnane-X-receptor and the vitamin D receptor (VDR), as well as the …
Conservation of an AE3 Cl <sup>−</sup> /HCO <sub>3</sub> <sup>−</sup> Exchanger Cardiac-Specific Exon and Promoter Region and AE3 mRNA Expression Patterns in Murine and Human Hearts
Authors: Stephen C. Linn, G. Roger Askew, Anil G. Menon, Gary E. Shull
Journal: Circulation Research (1995)

Abstract A cardiac-specific variant of the rat AE3 Cl − /HCO 3 − exchanger mRNA is transcribed from a promoter located in the sixth intron of a larger transcription unit expressed in brain and other tissues. The cardiac mRNA contains an alternative first exon encoding a 73–amino acid NH 2 -terminal sequence that replaces the first 270 amino acids of the brain AE3 variant. The present study was conducted to determine whether the cardiac-specific promoter region and exon are conserved in other species and to examine the expression patterns of AE3 mRNAs in adult tissues and during development. Analysis of murine and human genomic clones showed that both contain counterparts of the rat alternative exon. The cardiac promoter region is highly conserved in all three species and contains several potential transcription factor binding sites, including consensus MCAT and E-box sequences. Tissue-specific and developmental patterns of AE3 gene expression were examined by Northern blot hybridization. Mouse and human, like the rat, express both the 3.6-kb cardiac-specific AE3 mRNA and a 4.4-kb AE3 transcript found in brain, heart, and other tissues. Levels of the cardiac-specific transcript in mouse heart increase 17-fold between the fetal and adult stages, while the amount of the longer AE3 mRNA in heart decreases substantially. Furthermore, although the cardiac-specific mRNA is expressed in both atria and ventricles of mouse heart, the longer transcript is confined to the atria. These results suggest that the two AE3 variants have distinct roles in cardiac function and that the mechanisms regulating their expression are different.
Trans-Species Polymorphism and Allele-Specific Expression in the CBF Gene Family of Wild Tomatoes
Authors: Mamadou Mboup, Iris Fischer, Hilde Lainer, Wolfgang Stephan
Journal: Molecular Biology and Evolution (2012)

Abiotic stresses such as drought, extreme temperatures, and salinity have a strong impact on plant adaptation. They act as selective forces on plant physiology and morphology. These selective pressures leave characteristic footprints that can be detected at the DNA sequence level using population genetic tools. On the basis of a candidate gene approach, we investigated signatures of adaptation in two wild tomato species, Solanum peruvianum and S. chilense. These species are native to western South America and constitute a model system for studying adaptation, due to their ability to colonize diverse habitats and the available genetic resources. We have determined the selective forces acting on the C-repeat binding factor (CBF) gene family, which consists of three genes, and is known to be involved in tolerance to abiotic stresses, in particular in cold tolerance. We also analyzed the expression pattern of these genes after drought and cold stresses. We found that CBF3 evolves under very strong purifying selection, CBF2 is under balancing selection in some populations of both species (S. peruvianum/Quicacha and S. chilense/Nazca) maintaining a trans-species polymorphism, and CBF1 is a pseudogene. In contrast to previous studies of cultivated tomatoes showing that only CBF1 was cold induced, we found that all three CBF genes are cold induced in wild tomatoes. All three genes are also drought induced. CBF2 exhibits an allele-specific expression pattern associated with the trans-species polymorphism.
The changing phenotype of microglia from homeostasis to disease
Authors: Xiao-Guang Luo, Sheng-Di Chen
Journal: Translational Neurodegeneration (2012)

It has been nearly a century since the early description of microglia by Rio-Hortega; since then many more biological and pathological features of microglia have been recognized. Today, microglia are generally considered to be beneficial to homeostasis at the resting state through their abilities to survey the environment and phagocytose debris. However, when activated microglia assume diverse phenotypes ranging from fully inflamed, which involves the release of many pro-inflammatory cytokines, to alternatively activated, releasing anti-inflammatory cytokines or neurotrophins, the consequences to neurons can range from detrimental to supportive. Due to the different experimental sets and conditions, contradictory results have been obtained regarding the controversial question of whether microglia are “good” or “bad.” While it is well understood that the dual roles of activated microglia depend on specific situations, the underlying mechanisms have remained largely unclear, and the interpretation of certain findings related to diverse microglial phenotypes continues to be problematic. In this review we discuss the functions of microglia in neuronal survival and neurogenesis, the crosstalk between microglia and surrounding cells, and the potential factors that could influence the eventual manifestation of microglia.
Comparison Of Epitopes Between Ara h1 And Soybean Conglycinin (7s Globulin) And Ara h 3 And Glycinin G1/g2 Of Soybean (11s Globulin)
Authors: Y. Han, G.A. Grisina, W.G. Shreffler, R. Ayuso, J. Lin, L. Bardina, E. Wurmbach, H.A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2009)
Upregulation of Postbacteremic TNF- α and IL-1 α Gene Expression by Alveolar Hypoxia/Reoxygenation in Perfused Rat Lungs
Authors: GEORGE M. MATUSCHAK, CESAR F. MUNOZ, CHERYL A. JOHANNS, RASHID RAHMAN, ANDREW J. LECHNER
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Decreases in the alveolar O2 tension commonly follow gram-negative bacteremic shock that progresses to the acute respiratory distress syndrome (ARDS). To examine the effects of alveolar hypoxia and reoxygenation (H/R) on postbacteremic pulmonary cytokine expression, lungs from Sprague-Dawley rats (n = 43) were perfused over 180 min after hematogenous infection with 109 live Escherichia coli serotype O55:B5 (EC) or infusion of 0.9% NaCl (NS). Compared with normoxic EC and NS controls, EC + H/R and NS + H/R lungs received 90 min of constant-flow hypoxia followed by 60 min of reoxygenation. Perfusates were cultured and analyzed for TNF- α , IL-1 α , IL-1 β , and PGE2 while monitoring pulmonary artery pressure (Ppa). Changes in the filtration coefficient (Kf) were evaluated at 180 min when cytokine mRNA levels were assessed in lung homogenates. Transcripts of the anti-inflammatory cytokine TGF- β 1 and of inducible cyclooxygenase (COX-2) were similarly analyzed. For equivalent EC clearance, Ppa, and Kf as in normoxic EC, postbacteremic H/R increased TNF- α gene expression and doubled the export of TNF- α from the lungs, an effect not blocked by allopurinol. IL-1 α transcripts were also increased in EC + H/R versus EC lungs, in contrast to the lack of change in IL-1 β , TGF- β , or COX-2 mRNA levels, or in cell-associated or circulating IL-1 β and PGE2. Thus, gram-negative bacteremic lung infection and secondary alveolar H/R upregulate the expression of specific inflammatory cytokines compared with pulmonary infection under normoxic conditions, independently of xanthine oxidase-induced O2 radicals. These findings identify the alveolar Po 2 as a potent immunomodulatory signal whose reductions early after gram-negative sepsis may enhance lung inflammation in ARDS.
Autoimmune hepatitis – Update 2015
Authors: Michael P. Manns, Ansgar W. Lohse, Diego Vergani
Journal: Journal of Hepatology (2015)

AIH is a disease of unknown cause mainly occurring in women of all ages and races. The diagnosis is made based on clinical and laboratory criteria including specific circulating autoantibodies. Liver histology contributes to the diagnosis, its value mainly regarding grading and staging of damage and the exclusion of other morbidities or comorbidities. Our understanding of the molecular pathogenesis of AIH has improved in the last decades, including the identification of autoantigens at the molecular level as well as the function of TH1, TH2, and TH17 cells. In addition, GWAS in recent and upcoming years will help us to understand better disease susceptibility and may also help us to identify patients at particular risk. Therapies with corticosteroids alone, or in combination with azathioprine will be the SOC for the time being and will continue to save lives. Immunosuppressive drugs derived from transplantation medicine, like cyclosporin A, tacrolimus or MMF, offer an alternative for difficult to treat patients, novel more specific and safer immunosuppressive agents are urgently needed. Biological agents, like anti-TNF or anti-B cell antibodies, which interfere with important signal transduction pathways of the immune system have raised expectations within the AIH scientific community. Future therapies likely to enter clinical practice are the use of anti-CD3 or Tregs. However, our next goal is to eliminate AIH as an indication for liver transplantation. Here the end is at hand.
Precipitating causes of acid reflux episodes in ambulant patients with gastro-oesophageal reflux disease.
Authors: C P Barham, D C Gotley, A Mills, D Alderson
Journal: Gut (1995)

Previous studies of the mechanisms that precipitate acid reflux episodes have used short term hospital based measurements. A 24 hour pH and motility recording system, incorporating a sphincter monitoring device, has been developed to study naturally occurring acid reflux episodes in control subjects and patient groups with different grades of oesophagitis. Lower oesophageal sphincter relaxations related to episodes of acid reflux were common in control subjects (67% of episodes) but became more difficult to detect as the grade of oesophagitis increased (grade 0/1 - 67%, grade 2/3 - 35%, grade 4 - 13%). A variety of events that produced recognisable transdiaphragmatic pressure patterns were associated with acid reflux episodes. In control subjects 74% of acid reflux episodes were precipitated by belching but this mechanism became less evident as the grade of oesophagitis increased (grade 0/1 - 43%, grade 2/3 - 40%, grade 4 - 29%). Activities that produced a pressure gradient across the diaphragm became increasingly important as events precipitating acid reflux as oesophagitis became more severe (controls--2%, grade 0/1 - 15%, grade 2/3 - 11%, grade 4 - 22%). This study has shown the pressure events surrounding acid reflux in fully ambulant patients with gastro-oesophageal reflux disease.
Toward a Biology of Depression: Some Suggestions from Neurophysiology
Authors: P. C. WHYBROW, J. MENDELS
Journal: American Journal of Psychiatry (1969)

This review of recent research suggests the existence of an unstable state of central nervous system hyperexcitability in depression, and possibly in mania, with an associated but disorganized intrinsic hyperactivity. The authors propose this concept as a possible description of the prevailing neurophysiologic state of the individual with affective disorder and as complementary to other biological hypotheses currently under investigation. They conclude that the concept warrants further study, noting the need for replication and extension of many of the studies reviewed.
Health checks for people over 75.
Authors: D. O'Neill
Journal: BMJ (1992)

taken.'They also, however, noted a rise in the number of cases of homosexually acquired gonorrhoea in 1990, with a rate of rectal infection of 6 9%.In the three genitourinary medicine clinics in Riverside Health Authority 59 episodes of confirmed anorectal gonococcal infection occurred in 57 homosexual or bisexual men attending between 30 March and 8 October this year.Of these 57 men, 17 were known to be HIV seropositive and 19 HIV seronegative and 21 were untested for HIV antibodies.Thus while the rate of detection of rectal gonorrhoea in homosexual and bisexual men attending genitourinary medicine departments in this area is much lower than in the era before AIDS, there are no grounds for complacency as these men, regardless of their HIV status, are presumably continuing to have unprotected anal sex or failure of barrier methods.
Migration and maturation of Langerhans cells in skin transplants and explants.
Authors: C P Larsen, R M Steinman, M Witmer-Pack, D F Hankins, P J Morris, J M Austyn
Journal: The Journal of Experimental Medicine (1990)

The behavior of Langerhans cells (LC) has been examined after skin transplantation and in an organ culture system. Within 24 h (and even within 4 h of culture), LC in epidermal sheets from allografts, isografts, and explants dramatically increased in size and expression of major histocompatibility complex class II molecules, and their numbers were markedly decreased. Using a new procedure, dermal sheets were then examined. By 24 h, cells resembling LC were found close to the epidermal-dermal junction, and by 3 d, they formed cords in dermal lymphatics before leaving the skin. In organ culture, the cells continued to migrate spontaneously into the medium. These observations establish a direct route for migration of LC from the epidermis into the dermis and then out of the skin. These processes are apparently induced by a local inflammatory response, and are independent of host-derived mediators. The phenotype of migratory cells was then examined by two-color immunocytochemistry and FACS analysis. The majority of migratory leukocytes were Ia+ LC, the remainder comprised Thy-1+, CD3+, CD4-, CD8- presumptive T cell receptor gamma/delta+ dendritic epidermal cells, which clustered with the LC, and a small population of adherent Ia-, FcRII+, CD11a/18+ macrophages. In contrast to the cells remaining within the epidermis of grafted skin at 1 d, the migratory cells were heterogeneous in phenotype, particularly with respect to F4/80, FcRII, and interleukin 2 receptor alpha expression, which are useful markers to follow phenotypic maturation of LC. Moreover, cells isolated from the epidermis of grafts at 1 d were more immunostimulatory in the allogeneic mixed leukocyte reaction and oxidative mitogenesis than LC isolated from normal skin, though less potent than spleen cells. The day 1 migratory cells were considerably more immunostimulatory than spleen cells, and day 3-5 migratory cells even more so, suggesting that functional maturation continues in culture. Thus, maturation of LC commences in the epidermis and continues during migration, but the cells do not need to be fully mature in phenotype or function before they leave the skin. In vivo, the migration of epidermal LC via the dermis into lymphatics and then to the draining nodes, where they have been shown previously to home to T areas, would provide a powerful stimulus for graft rejection.
High-Dose Rifapentine with Moxifloxacin for Pulmonary Tuberculosis
Authors: Amina Jindani, Thomas S. Harrison, Andrew J. Nunn, Patrick P.J. Phillips, Gavin J. Churchyard, Salome Charalambous, Mark Hatherill, Hennie Geldenhuys, Helen M. McIlleron, Simbarashe P. Zvada, Stanley Mungofa, Nasir A. Shah, Simukai Zizhou, Lloyd Magweta, James Shepherd, Sambayawo Nyirenda, Janneke H. van Dijk, Heather E. Clouting, David Coleman, Anna L.E. Bateson, Timothy D. McHugh, Philip D. Butcher, Denny A. Mitchison
Journal: New England Journal of Medicine (2014)

Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed.