tbuckley/cabot-search huggingface dataset:
Nature of the Gap Phenomenon in Man
Authors: DELON WU, PABLO DENES, RAMESH DHINGRA, KENNETH M. ROSEN
Journal: Circulation Research (1974)

The atrioventricular (AV) gap phenomenon occurs when the effective refractory period of a distal site is longer than the functional refractory period of a proximal site and when closely coupled stimuli are delayed enough at the proximal site to allow distal site recovery. According to previous studies, in type 1 gap, the distal site of block is distal to the His bundle (ventricular specialized conduction system) and the proximal site of block is in the AV node. In type 2 gap, both the proximal and the distal sites of conduction block are within the ventricular specialized conduction system. Using His bundle recordings and atrial extra-stimulus techniques in man, we observed three previously undescribed types of gaps between (1) the AV node (distal) and the atrium (proximal), (2) the His bundle (distal) and the AV node (proximal), and (3) the ventricular specialized conduction system or a bundle branch (distal) and the His bundle (proximal). The delays at the His bundle in the second and third types of gaps seen in this study were demonstrated as splitting of His bundle potentials. Gaps between the AV node or the His bundle and the ventricular specialized conduction system were more easily demonstrated at long cycle lengths, but gaps between the atrium and the AV node were more easily demonstrated at short cycle lengths. Therefore, the previous subdivision of gaps into two types is an oversimplification, because gaps can occur between multiple sites in the conduction system. The gap phenomenon may be potentiated by both long and short cycle lengths; long cycle lengths increase the effective refractory period of a distal site, e.g., the His bundle and the ventricular specialized conduction system, and the short cycle lengths decrease the functional refractory period of a proximal site, e.g., the atrium and the AV node.
A Locus for Renal Malformations Including Vesico-Ureteric Reflux on Chromosome 13q33–34
Authors: Kalyani R. Vats, Chandra Ishwad, Ish Singla, Ashutosh Vats, Robert Ferrell, Demetrius Ellis, Michael Moritz, Urvashi Surti, Parul Jayakar, Donald R. Frederick, Abhay N. Vats
Journal: Journal of the American Society of Nephrology (2006)

Congenital anomalies of kidney and urinary tract (CAKUT), including vesico-ureteric reflux (VUR), are major causes of ESRD in childhood. Herein is reported evidence for a locus on 13q33q34 associated with CAKUT. Deletion mapping of chromosome 13q was performed in four children with CAKUT using 31 microsatellite markers on peripheral blood genomic DNA that was obtained from the patients and their parents. mRNA expression of the positional candidate genes was compared with sequences in electronic databases in silico and also studied in adult and fetal mouse kidneys using reverse transcription–PCR. The children (three girls; age range 5 to 17 yr) had varying severity of developmental delay and other organ system involvement. The spectrum of CAKUT included high-grade VUR (n = 2), renal dysplasia (n = 2), and hydronephrosis (n = 1). Both the children with VUR had evidence of renal failure with one of them developing ESRD. Deletion mapping identified a 7-Mb critical region flanked by markers D13S1311 and D13S285. There are 33 genes (12 known; 21 computer predicted) in this region. In silico expression studies showed matches for 14 of these genes in the kidneys and 10 in the bladder expressed sequenced tags databases. Mouse kidney studies showed that of the 24 genes examined, several had variable expression through the different stages of renal development, whereas five of the genes were not expressed at all. Herein is reported a new locus on chromosome 13q33q34 that can be associated with VUR with several genes showing mRNA expression patterns that suggest their potential for involvement in renal/urinary tract developmental anomalies.
Expression of xenotropic murine leukemia viruses as cell-surface gp70 in genetic crosses between strains DBA/2 and C57BL/6.
Authors: H C Morse, T M Chused, J W Hartley, B J Mathieson, S O Sharrow, B A Taylor
Journal: The Journal of Experimental Medicine (1979)

Flow microfluorometry was used to assess levels of xenotropic murine leukemia virus envelope-related cell-surface antigens (XenCSA) expressed on lymphocytes of mice derived from crosses between C57BL/6 (B6) and DBA/2 (D2); 24 recombinant inbred strains (BXD RIs) and 62 backcross mice were studied. The results suggest that XenCSA expression is affected by more than one gene but that the predominant influence is exerted by a single semidominant gene apparently located on chromosome 4 at or in close proximity to the Fv-1 locus. Studies of spontaneous virus production in B6D2F1 X D2 mice suggest that this locus may also affect production by spleen cells of xenotropic MuLV registering in a fluorescent antibody assay of mink lung cells.
Robert Gordon Pickard
Authors: J. P. D. Reid.
Journal: BMJ (2013)

Robert Gordon Pickard had a distinguished undergraduate career, won the Hallett prize in the primary fellowship and secured both the MRCP and FRCS while working in junior posts in London, Stoke, Chester, and the Birmingham Accident Hospital. He spent two years in neurosurgery at the Atkinson Morley’s Hospital, Queen Square, and …
Salsalate Improves Glycemia and Inflammatory Parameters in Obese Young Adults
Authors: Amy Fleischman, Steven E. Shoelson, Raquel Bernier, Allison B. Goldfine
Journal: Diabetes Care (2008)

Sedentary lifestyle and a western diet promote subacute-chronic inflammation, obesity, and subsequently dysglycemia. The aim of the current study was to evaluate the efficacy of the anti-inflammatory drug salsalate to improve glycemia by reducing systemic inflammation in obese adults at risk for the development of type 2 diabetes.In a double-masked, placebo controlled trial, we evaluated 20 obese nondiabetic adults at baseline and after 1 month of salsalate or placebo.Compared with placebo, salsalate reduced fasting glucose 13% (P < 0.002), glycemic response after an oral glucose challenge 20% (P < 0.004), and glycated albumin 17% (P < 0.0003). Although insulin levels were unchanged, fasting and oral glucose tolerance test C-peptide levels decreased in the salsalate-treated subjects compared with placebo (P < 0.03), consistent with improved insulin sensitivity and a known effect of salicylates to inhibit insulin clearance. Adiponectin increased 57% after salsalate compared with placebo (P < 0.003). Additionally, within the group of salsalate-treated subjects, circulating levels of C-reactive protein were reduced by 34% (P < 0.05).This proof-of-principle study demonstrates that salsalate reduces glycemia and may improve inflammatory cardiovascular risk indexes in overweight individuals. These data support the hypothesis that subacute-chronic inflammation contributes to the pathogenesis of obesity-related dysglycemia and that targeting inflammation may provide a therapeutic route for diabetes prevention.
Anemia- and polycythemia-inducing isolates of Friend spleen focus-forming virus. Biological and molecular evidence for two distinct viral genomes.
Authors: M E MacDonald, F H Reynolds, W J Van de Ven, J R Stephenson, T W Mak, A Bernstein
Journal: The Journal of Experimental Medicine (1980)

Two distinct clones of Friend spleen focus-forming virus (SFFV), differing in their erythroleukemic potential, are described. These isolates have been cloned free of their associated helper viruses and shown to be replication-defective. Both SFFV isolates have been rescued from rat fibroblast nonproducer cell clones with cloned replication-competent viruses, F-MuLVA and F-MuLVP, obtained from the anemia- or polycythemia-inducing isolates of Friend virus complex, respectively. These rescued viruses induce a rapid proliferative disease associated with the appearance of macroscopic spleen foci and splenomegaly. In addition, each is subject to regulation by the W, Steel (Sl), and Fv-2 host gene loci. These two isolates of SFFV can, however, be distinguished by both biological and molecular criteria. Friend SFFVP induces a rapid polycythemia associated with the appearance of large numbers of erythropoietin (EPO)-independent erythroid colony-forming cells in the marrow and spleen. In contrast, SFFVA induces a rapid anemia associated with a progressive decrease in the number of EPO-dependent erythroid colony-forming cells in marrow, and a rapid increase in the number of EPO-dependent erythroid colony-forming cells in spleen. Furthermore, the nature of the disease induced by the two isolates of SFFV is independent of the Friend helper virus: SFFVP, rescued from a nonproducer cell clone with either F-MuLVA or F0MuLVP, induced a polycythemic transformation, whereas SFFVA, rescued with either F-MuLVA or F-MuLVP, induced an anemic transformation. The two Friend SFFV isolates can also be discriminated on the basis of translational products encoded by their gag and env genes: SFFVP encodes the amino-terminal gag-gene protein p15, whereas SFFVA encodes the gag-gene proteins p15, p12, and p30. In addition, the SFFV isolates encode nonidentical 55,000-mol wt env gene-related proteins that can be distinguished by analysis of their methionine-containing tryptic peptides.
High Proportions of Deleterious Polymorphisms in Constrained Human Genes
Authors: S. Subramanian
Journal: Molecular Biology and Evolution (2010)

Previous studies on human mitochondrial genomes showed that the ratio of intra-specific diversities at nonsynonymous-to-synonymous positions was two to ten times higher than the ratio of interspecific divergences at these positions, suggesting an excess of slightly deleterious nonsynonymous polymorphisms. However, such an overabundance of nonsynonymous single nucleotide polymorphisms (SNPs) was not found in human nuclear genomes. Here, genome-wide estimates using >14,000 human–chimp nuclear genes and 1 million SNPs from four human genomes showed a significant proportion of deleterious nonsynonymous SNPs (∼15%). Importantly, this study reveals a negative correlation between the magnitude of selection pressure and the proportion of deleterious SNPs on human genes. The proportion of deleterious amino acid replacement polymorphisms is 3.5 times higher in genes under high purifying selection compared with that in less constrained genes (28% vs. 8%). These results are explained by differences in the extent of contribution of mildly deleterious mutations to diversity and substitution.
The impact of ageing and sex on the association between sleepiness and sleep disordered breathing
Authors: Mary J. Morrell, Laurel Finn, Alison McMillan, Paul E. Peppard
Journal: European Respiratory Journal (2012)

The aim of our study was to investigate age-related changes in sleepiness symptoms associated with sleep disordered breathing (SDB). Wisconsin Sleep Cohort participants were assessed using polysomnography, the Epworth Sleepiness Scale (ESS) and the multiple sleep latency test (MSLT). SDB was defined as an apnoea/hypopnoea index ≥15 events·h(-1), and sleepiness as ESS ≥10 and MSLT ≤5 min. Odds ratios were calculated using generalised estimating equations associating sleepiness with SDB, and conditional logistic regression examining changes in longitudinal sleepiness status (ESS only). Models were a priori stratified by sex. ESS was measured in 1,281 participants and MSLT in 998 at multiple time-points (ESS n=3,695; MSLT n=1,846). Significant interactions were found between SDB and age in males, but not females. The odds ratios modelled for sleepiness in a 40-yr-old male with SDB were significant compared to a male without SDB (ESS 2.1 and MSLT 2.9); however, these associations were not significant at 60 yrs of age. The within-subject odds ratio for sleepiness was also significant at 40 yrs of age (OR 3.4), but not at 60 yrs of age. The age-related reductions in the association between sleepiness and SDB may have clinical implications for the diagnosis and treatment of SDB in older people as sleepiness is often used as a therapeutic target.
The estimation of oxygen consumption
Authors: C. G. LaFarge, O. S. Miettinen
Journal: Cardiovascular Research (1970)

Journal Article The estimation of oxygen consumption Get access C. G. LaFarge, C. G. LaFarge 2 From the Children's Hospital Medical Center, Boston, Massachusetts, U.S.A. 2Present address: Cardiology Division, Department of Medicine, Children's Hospital Medical Center, Boston and the Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar O. S. Miettinen O. S. Miettinen From the Children's Hospital Medical Center, Boston, Massachusetts, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 4, Issue 1, January 1970, Pages 23–30, https://doi.org/10.1093/cvr/4.1.23 Published: 01 January 1970 Article history Accepted: 19 August 1969 Published: 01 January 1970
Current fluctuations and oscillations in smooth muscle cells from hog carotid artery. Role of the sarcoplasmic reticulum.
Authors: M Désilets, S P Driska, C M Baumgarten
Journal: Circulation Research (1989)

Electrical activity of enzymatically isolated, smooth muscle cells from hog carotid arteries was recorded under current clamp and voltage clamp. Under the experimental conditions, membrane potential usually was not stable, and spontaneous hyperpolarizing transients of approximately 100-msec duration were recorded. The amplitude of the transients was markedly voltage dependent and ranged from about 20 mV at a membrane potential of 0 mV to undetectable at membrane potentials negative to -60 mV. Under voltage clamp, transient outward currents displayed a similar voltage dependency. These fluctuations reflect a K+ current; they were abolished by 10 mM tetraethylammonium chloride, a K+ channel blocker, and the current fluctuations reversed direction in high extracellular K+ concentration. Modulators of intracellular Ca2+ concentration also affected electrical activity. Lowering intracellular Ca2+ concentration by addition of 10 mM EGTA to the pipette solution or suppressing sarcoplasmic reticulum function by superfusion with caffeine (10 mM), ryanodine (1 microM), or histamine (3-10 microM) blocked the rapid voltage and current spikes. However, caffeine and histamine induced a much slower hump of outward current before blocking the rapid spikes. This slower transient outward current could be elicited only once after external Ca2+ was removed and is consistent with an activation of K+ channels by Ca2+ released from internal stores. In contrast, removal of external Ca2+ alone failed to abolish the rapid spikes. These results suggest that 1) a Ca2+-dependent K+ conductance can markedly affect the electrical behavior of arterial smooth muscle cells and 2) internal Ca2+ stores, probably the sarcoplasmic reticulum, can support rapid and frequent releases of Ca2+. Exposure to a low concentration of histamine (3 microM) caused synchronization of the irregular, rapid fluctuations giving rise to slow, periodic oscillations of Ca2+-activated K+ conductance with a frequency of 0.1-0.3 Hz. These regular oscillations are reminiscent of periodic Ca2+-induced Ca2+ release, were inhibited by 10 mM caffeine, and point to a modulation of sarcoplasmic reticulum Ca2+ release by histamine.
Epidemiology of rhinitis in Portugal: evaluation of the intermittent and the persistent types
Authors: A. Todo‐Bom, C. Loureiro, M. M. Almeida, C. Nunes, L. Delgado, G. Castel‐Branco, J. Bousquet
Journal: Allergy (2007)

Background: The prevalence of rhinitis is rapidly increasing in recent years and has become a major public health problem in developed countries. A new classification of allergic rhinitis has been proposed by the allergic rhinitis and its impact on asthma group. In this study we aimed to evaluate the prevalence of rhinitis, including different rhinitis subtypes and to describe the severity, rate of diagnosis and use of medication in this pathology. Methods: A cross‐sectional, population‐based study including 6859 questionnaire responses was performed. Results: The estimated prevalence of rhinitis was 26.1% (48% for intermittent vs 52% for persistent rhinitis). Only about one‐third of the rhinitis cases (31.9%) had done skin prick tests (35.3% for persistent rhinitis vs 21.5% for intermittent rhinitis: P &lt; 0.001) or had medication prescribed in the last year (34%), (35.6% for persistent rhinitis vs 20.1% for intermittent rhinitis : P &lt; 0.001). The prevalence of rhinitis was higher in women (28.2 vs 22.2%; P &lt; 0.001). Intermittent/persistent rhinitis showed the following percentages : ≤25 years (65.6 vs 34.5, P = 0.001); 25–65 years (50.2 vs 49.5) ≥ 65 years (52.1 vs 47.9). The estimated prevalence of rhino conjunctivitis was 18.4%. In a severity scale from 0 to 10, the mean value was 6.1 points (6.4 for persistent rhinitis vs 4.8 for intermittent rhinitis: P &lt; 0.001). Conclusion: A significant prevalence of rhinitis and rhino conjunctivitis was identified in all age groups. The severity, the frequency and duration of the symptoms which classify the persistent type should be considered to establish a more effective treatment and improve the quality of life of the patients with rhinitis.
The presence of total knee or hip replacements due to osteoarthritis enhances the positive association between hand osteoarthritis and atherosclerosis in women: the AGES–Reykjavik study
Authors: Helgi Jonsson, Gudrun P Helgadottir, Thor Aspelund, Gudny Eiriksdottir, Sigurdur Sigurdsson, Kristin Siggeirsdottir, Thorvaldur Ingvarsson, Tamara B Harris, Lenore Launer, Vilmundur Gudnason
Journal: Annals of the Rheumatic Diseases (2011)

Objective This study examines the relationship between total knee replacements (TKR), total hip replacements (THR) or replacements of either joint (total joint replacement; TJR) due to osteoarthritis and atherosclerosis in a large population-based study. Methods The participants were 2195 men and 2975 women, mean age 76±6 years. The osteoarthritis data were analysed in relation to measures of atherosclerosis, including carotid artery intima media thickness and plaque severity (ultrasound), coronary and aortic calcifications (CT), cerebral white matter lesions (MRI) and a history of previous cardiac and cerebral events. Results The prevalence of TKR was 223 (4.3%) and THR 316 (6.1%). The presence of TJR in women was associated with a non-significant trend towards increased carotid plaque severity, coronary calcifications and periventricular white matter hyperintensities (PVH) but not with a history of cardiac or cerebral events. No associations were seen in men. When TJR were grouped according to the presence or absence of hand osteoarthritis (HOA) there was a highly significant association in the order −TJR/−HOA &lt; +TJR/−HOA &lt; −TJR/+HOA &lt; +TJR/+HOA, for carotid plaque severity, coronary calcifications and PVH. Conclusion The presence of TJR did not show a significant independent association with atherosclerosis but enhanced the strength of the positive association between HOA and subclinical atherosclerosis in women.
Maize and Risk of Cancers of the Oral Cavity, Pharynx, and Esophagus in Northeastern Italy
Authors: S. Franceschi, E. Bidoli, A. E. Baron, C. La Vecchia
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Maize and Risk of Cancers of the Oral Cavity, Pharynx, and Esophagus in Northeastern Italy Get access Silvia Franceschi, Silvia Franceschi * Epidemiology Unit, Aviano Cancer CenterAviano (PN), ItalyHormones, Sexual Factors & Cancer Group-European Organization for Cooperation in Cancer Prevention StudiesBruxelles, Belgium *Correspondence to : Silvia Franceschi, M.D., Epidemiology Unit, Aviano Cancer Center, Via Pedemontana Occ., 33081 Aviano (PN), Italy. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ettore Bidoli, Ettore Bidoli Epidemiology Unit, Aviano Cancer CenterAviano (PN), Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Anna E. Barón, Anna E. Barón Epidemiology Unit, Aviano Cancer CenterAviano (PN), ItalyDepartment of Preventive Medicine and Biometrics, University of ColoradoDenver, Colo Search for other works by this author on: Oxford Academic PubMed Google Scholar Carlo La Vecchia Carlo La Vecchia “Mario Negri” Institute for Pharmacological ResearchMilan, ItalyInstitute of Social and Preventive Medicine, University of LausanneLausanne, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 17, 5 September 1990, Pages 1407–1411, https://doi.org/10.1093/jnci/82.17.1407 Published: 05 September 1990 Article history Received: 04 April 1990 Revision received: 11 June 1990 Accepted: 15 June 1990 Published: 05 September 1990
Selection of macrophage-resistant progressor tumor variants by the normal host. Requirement for concomitant T cell-mediated immunity.
Authors: J L Urban, H Schreiber
Journal: The Journal of Experimental Medicine (1983)

The ultraviolet radiation-induced fibrosarcoma 1591 is generally rejected by normal syngeneic mice, but occasionally the tumor succeeds in growing progressively. Analysis of these progressively growing tumors has regularly demonstrated the development of tumor variants that have acquired a heritable progressive growth potential. We have analyzed the phenotypic changes of these variants to determine which kind of selection pressure had occurred during the evolution of the variants, thus giving insight into the relative importance and hierarchy of the different immune defense mechanisms that may be operating in normal individuals as a defense against neoplastic cells. We discovered that all of the host-selected progressor variants had lost not only a strong T cell-recognized and tumor-specific antigen, but also their high sensitivity to cytotoxic macrophages. No selection for macrophage-resistance or loss of the tumor antigen was observed in 1591 tumors reisolated from idiotypically-suppressed mice or from other mice lacking tumor-specific T cell immunity. Analysis of other tumor variants selected in vitro showed that 1591 tumor cells have the potential to lose sensitivity to tumoricidal macrophages without losing the T cell-recognized tumor antigen. Thus the data suggest that T cells and macrophages act together to suppress the outgrowth of potentially malignant cells in vivo.
Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-<i>Fcgr2b</i> <b>−</b>/<b>−</b> <i>Pdcd1</i> <b>−</b>/<b>−</b> mice
Authors: Taku Okazaki, Yumi Otaka, Jian Wang, Hiroshi Hiai, Toshiyuki Takai, Jeffrey V. Ravetch, Tasuku Honjo
Journal: The Journal of Experimental Medicine (2005)

Because most autoimmune diseases are polygenic, analysis of the synergistic involvement of various immune regulators is essential for a complete understanding of the molecular pathology of these diseases. We report the regulation of autoimmune diseases by epistatic effects of two immunoinhibitory receptors, low affinity type IIb Fc receptor for IgG (FcγRIIB) and programmed cell death 1 (PD-1). Approximately one third of the BALB/c-Fcgr2b−/−Pdcd1−/− mice developed autoimmune hydronephrosis, which is not observed in either BALB/c-Fcgr2b−/− or BALB/c-Pdcd1−/− mice. Hydronephrotic mice produced autoantibodies (autoAbs) against urothelial antigens, including uroplakin IIIa, and these antibodies were deposited on the urothelial cells of the urinary bladder. In addition, ∼15% of the BALB/c-Fcgr2b−/−Pdcd1−/− mice produced antinuclear autoAbs. In contrast, the frequency of the autoimmune cardiomyopathy and the production of anti–parietal cell autoAb, which were observed in BALB/c-Pdcd1−/− mice, were not affected by the additional FcγRIIB deficiency. These observations suggest cross talk between two immunoinhibitory receptors, FcγRIIB and PD-1, on the regulation of autoimmune diseases.